Enzyme Nomenclature

Continued from EC 1.14.13.151 to EC 1.14.13.238

EC 1.14.14 to EC 1.14.21

Sections

EC 1.14 Acting on paired donors with incorporation of molecular oxygen [continued]
EC 1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
EC 1.14.15 With a reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
EC 1.14.16 With reduced pteridine as one donor, and incorporation of one atom of oxygen
EC 1.14.17 With ascorbate as one donor, and incorporation of one atom of oxygen
EC 1.14.18 With another compound as one donor, and incorporation of one atom of oxygen
EC 1.14.19 With oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water
EC 1.14.20 With 2-oxoglutarate as one donor, and the other dehydrogenated
EC 1.14.21 With NADH or NADPH as one donor, and the other dehydrogenated


EC 1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.14.1 unspecific monooxygenase
EC 1.14.14.2 deleted, included in EC 1.14.14.1
EC 1.14.14.3 bacterial luciferase
EC 1.14.14.4 deleted, identical to EC 1.14.15.7
EC 1.14.14.5 alkanesulfonate monooxygenase
EC 1.14.14.6 transferred now EC 1.14.13.111
EC 1.14.14.7 transferred now EC 1.14.19.9
EC 1.14.14.8 anthranilate 3-monooxygenase (FAD)
EC 1.14.14.9 4-hydroxyphenylacetate 3-monooxygenase
EC 1.14.14.10 nitrilotriacetate monooxygenase
EC 1.14.14.11 styrene monooxygenase
EC 1.14.14.12 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione monooxygenase
EC 1.14.14.13 4-(L-γ-glutamylamino)butanoyl-[BtrI acyl-carrier protein] monooxygenase
EC 1.14.14.14 aromatase
EC 1.14.14.15 (3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] monooxygenase
EC 1.14.14.16 steroid 21-monooxygenase
EC 1.14.14.17 squalene monooxygenase
EC 1.14.14.18 heme oxygenase (biliverdin-producing)
EC 1.14.14.19 steroid 17α-monooxygenase
EC 1.14.14.20 phenol 2-monooxygenase (FADH2)
EC 1.14.14.21 dibenzothiophene monooxygenase
EC 1.14.14.22 dibenzothiophene sulfone monooxygenase
EC 1.14.14.23 cholesterol 7α-monooxygenase
EC 1.14.14.24 vitamin D 25-hydroxylase
EC 1.14.14.25 cholesterol 24-hydroxylase
EC 1.14.14.26 24-hydroxycholesterol 7α-hydroxylase
EC 1.14.14.27 resorcinol 4-hydroxylase (FADH2)
EC 1.14.14.28 long-chain alkane monooxygenase
EC 1.14.14.29 25/26-hydroxycholesterol 7α-hydroxylase
EC 1.14.14.30 isobutylamine N-monooxygenase
EC 1.14.14.31 ipsdienol synthase
EC 1.14.14.32 17α-hydroxyprogesterone deacetylase
EC 1.14.14.33 ethylenediaminetetraacetate monooxygenase
EC 1.14.14.34 methanesulfonate monooxygenase (FMNH2)
EC 1.14.14.35 dimethylsulfone monooxygenase
EC 1.14.14.36 tyrosine N-monooxygenase
EC 1.14.14.37 4-hydroxyphenylacetaldehyde oxime monooxygenase
EC 1.14.14.38 valine N-monooxygenase
EC 1.14.14.39 isoleucine N-monooxygenase
EC 1.14.14.40 phenylalanine N-monooxygenase
EC 1.14.14.41 (E)-2-methylbutanal oxime monooxygenase
EC 1.14.14.42 homomethionine N-monooxygenase
EC 1.14.14.43 (methylthio)alkanaldoxime N-monooxygenase
EC 1.14.14.44 phenylacetaldehyde oxime monooxygenase
EC 1.14.14.45 aromatic aldoxime N-monooxygenase
EC 1.14.14.46 pimeloyl-[acyl-carrier protein] synthase
EC 1.14.14.47 nitric-oxide synthase (flavodoxin)
EC 1.14.14.48 jasmonoyl-L-amino acid 12-hydroxylase
EC 1.14.14.49 12-hydroxyjasmonoyl-L-amino acid 12-hydroxylase
EC 1.14.14.50 tabersonine 3-oxygenase
EC 1.14.14.51 (S)-limonene 6-monooxygenase
EC 1.14.14.52 (S)-limonene 7-monooxygenase
EC 1.14.14.53 (R)-limonene 6-monooxygenase
EC 1.14.14.54 phenylacetate 2-hydroxylase

EC 1.14.14.1

Accepted name: unspecific monooxygenase

Reaction: RH + [reduced NADPH-hemoprotein reductase] + O2 = ROH + [oxidized NADPH-hemoprotein reductase] + H2O

Other name(s): microsomal monooxygenase; xenobiotic monooxygenase; aryl-4-monooxygenase; aryl hydrocarbon hydroxylase; microsomal P-450; flavoprotein-linked monooxygenase; flavoprotein monooxygenase

Systematic name: substrate,reduced-flavoprotein:oxygen oxidoreductase (RH-hydroxylating or -epoxidizing)

Comments: A group of P-450 heme-thiolate proteins, acting on a wide range of substrates including many xenobiotics, steroids, fatty acids, vitamins and prostaglandins; reactions catalysed include hydroxylation, epoxidation, N-oxidation, sulfooxidation, N-, S- and O-dealkylations, desulfation, deamination, and reduction of azo, nitro and N-oxide groups. Together with EC 1.6.2.4, NADPH—hemoprotein reductase, it forms a system in which two reducing equivalents are supplied by NADPH. Some of the reactions attributed to EC 1.14.15.3, alkane 1-monooxygenase, belong here.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, UM-BBD, CAS registry number: 9038-14-6

References:

1. Booth, J. and Boyland, E. The biochemistry of aromatic amines. 3. Enzymic hydroxylation by rat-liver microsomes. Biochem. J. 66 (1957) 73-78. [PMID: 13426111]

2. Fujita, T. and Mannering, G.J. Differences in soluble P-450 hemoproteins from livers of rats treated with phenobarbital and 3-methylcholanthrene. Chem. Biol. Interact. 3 (1971) 264-265. [PMID: 5132997]

3. Haugen, D.A. and Coon, M.J. Properties of electrophoretically homogeneous phenobarbital-inducible and β-naphthoflavone-inducible forms of liver microsomal cytochrome P-450. J. Biol. Chem. 251 (1976) 7929-7939. [PMID: 187601]

4. Imaoka, S., Inoue, K. and Funae, Y. Aminopyrine metabolism by multiple forms of cytochrome P-450 from rat liver microsomes: simultaneous quantitation of four aminopyrine metabolites by high-performance liquid chromatography. Arch. Biochem. Biophys. 265 (1988) 159-170. [PMID: 3415241]

5. Johnson, E.F., Zounes, M. and Müller-Eberhard, U. Characterization of three forms of rabbit microsomal cytochrome P-450 by peptide mapping utilizing limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. Arch. Biochem. Biophys. 192 (1979) 282-289. [PMID: 434823]

6. Kupfer, D., Miranda, G.K., Navarro, J., Piccolo, D.E. and Theoharides, A.D. Effect of inducers and inhibitors of monooxygenase on the hydroxylation of prostaglandins in the guinea pig. Evidence for several monooxygenases catalyzing ω- and ω-1-hydroxylation. J. Biol. Chem. 254 (1979) 10405-10414. [PMID: 489601]

7. Lang, M.A., Gielen, J.E. and Nebert, D.W. Genetic evidence for many unique liver microsomal P-450-mediated monooxygenase activities in heterogeneic stock mice. J. Biol. Chem. 256 (1981) 12068-12075. [PMID: 7298645]

8. Lang, M.A. and Nebert, D.W. Structural gene products of the Ah locus. Evidence for many unique P-450-mediated monooxygenase activities reconstituted from 3-methylcholanthrene-treated C57BL/6N mouse liver microsomes. J. Biol. Chem. 256 (1981) 12058-12075. [PMID: 7298644]

9. Leo, M.A., Lasker, J.M., Rauby, J.L., Kim, C.I., Black, M. and Lieber, C.S. Metabolism of retinol and retinoic acid by human liver cytochrome P450IIC8. Arch. Biochem. Biophys. 269 (1989) 305-312. [PMID: 2916844]

10. Lu, A.Y.H., Kuntzman, S.W., Jacobson, M. and Conney, A.H. Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds, and endogenous substrates. II. Role of the cytochrome P-450 and P-448 fractions in drug and steroid hydroxylations. J. Biol. Chem. 247 (1972) 1727-1734. [PMID: 4401153]

11. Mitoma, C., Posner, H.S., Reitz, H.C. and Udenfriend, S. Enzymic hydroxylation of aromatic compounds. Arch. Biochem. Biophys. 61 (1956) 431-441. [PMID: 13314626]

12. Mitoma, C. and Udenfriend, S. Aryl-4-hydroxylase. Methods Enzymol. 5 (1962) 816-819.

13. Napoli, J.L., Okita, R.T., Masters, B.S. and Horst, R.L. Identification of 25,26-dihydroxyvitamin D3 as a rat renal 25-hydroxyvitamin D3 metabolite. Biochemistry 20 (1981) 5865-5871. [PMID: 7295706]

14. Nebert, D.W. and Gelboin, H.V. Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. I. Assay and properties of induced enzyme. J. Biol. Chem. 243 (1968) 6242-6249. [PMID: 4387094]

15. Suhara, K., Ohashi, K., Takahashi, K. and Katagiri, M. Aromatase and nonaromatizing 10-demethylase activity of adrenal cortex mitochondrial P-450(11)beta. Arch. Biochem. Biophys. 267 (1988) 31-37. [PMID: 3264134]

16. Theoharides, A.D. and Kupfer, D. Evidence for different hepatic microsomal monooxygenases catalyzing ω- and (ω-1)-hydroxylations of prostaglandins E1 and E2. Effects of inducers of monooxygenase on the kinetic constants of prostaglandin hydroxylation. J. Biol. Chem. 256 (1981) 2168-2175. [PMID: 7462235]

17. Thomas, P.E., Lu, A.Y.H., Ryan, D., West, S.B., Kawalek, J. and Levin, W. Immunochemical evidence for six forms of rat liver cytochrome P450 obtained using antibodies against purified rat liver cytochromes P450 and P448. Mol. Pharmacol. 12 (1976) 746-758. [PMID: 825720]

[EC 1.14.14.1 created 1961 as EC 1.99.1.1, transferred 1965 to EC 1.14.1.1, transferred 1972 to EC 1.14.14.1 (EC 1.14.14.2 created 1972, incorporated 1976, EC 1.14.99.8 created 1972, incorporated 1984), modified 2015]

[EC 1.14.14.2 Deleted entry: benzopyrene 3-monooxygenase. Now included with EC 1.14.14.1 unspecific monooxygenase (EC 1.14.14.2 created 1972, deleted 1976)]

EC 1.14.14.3

Accepted name: bacterial luciferase

Reaction: a long-chain aldehyde + FMNH2 + O2 = a long-chain fatty acid + FMN + H2O +

Other name(s): aldehyde monooxygenase; luciferase; Vibrio fischeri luciferase; alkanal,reduced-FMN:oxygen oxidoreductase (1-hydroxylating, luminescing); alkanal,FMNH2:oxygen oxidoreductase (1-hydroxylating, luminescing); alkanal monooxygenase (FMN); aldehyde,FMNH2:oxygen oxidoreductase (1-hydroxylating, luminescing)

Systematic name: long-chain-aldehyde,FMNH2:oxygen oxidoreductase (1-hydroxylating, luminescing)

Comments: The reaction sequence starts with the incorporation of a molecule of oxygen into reduced FMN bound to the enzyme, forming luciferase peroxyflavin. The peroxyflavin interacts with an aliphatic long-chain aldehyde, producing a highly fluorescent species believed to be luciferase hydroxyflavin. The enzyme is highly specific for reduced FMN and for long-chain aliphatic aldehydes with eight carbons or more. The highest efficiency is achieved with tetradecanal. cf. EC 1.13.12.18, dinoflagellate luciferase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9014-00-0

References:

1. Hastings, J.W. and Nealson, K.H. Bacterial bioluminescence. Annu. Rev. Microbiol. 31 (1977) 549-595. [PMID: 199107]

2. Hastings, J.W. Bacterial bioluminescence light emission in the mixed function oxidation of reduced flavin and fatty aldehyde. Crit. Rev. Biochem. 5 (1978) 163-184. [PMID: 363350]

3. Hastings, J.W. and Presswood, R.P. Bacterial luciferase: FMNH2-aldehyde oxidase. Methods Enzymol. 53 (1978) 558-570. [PMID: 309549]

4. Nealson, K.H. and Hastings, J.W. Bacterial bioluminescence: its control and ecological significance. Microbiol. Rev. 43 (1979) 496-518. [PMID: 396467]

5. Suzuki, K., Kaidoh, T., Katagiri, M. and Tsuchiya, T. O2 incorporation into a long-chain fatty-acid during bacterial luminescence. Biochim. Biophys. Acta 722 (1983) 297-301.

6. Kurfurst, M., Ghisla, S. and Hastings, J.W. Characterization and postulated structure of the primary emitter in the bacterial luciferase reaction. Proc. Natl. Acad. Sci. USA 81 (1984) 2990-2994. [PMID: 16593462]

[EC 1.14.14.3 created 1981, modified 2016]

[EC 1.14.14.4 Deleted entry: choline monooxygenase. Identical to EC 1.14.15.7 (EC 1.14.14.4 created 2000, deleted 2002)]

EC 1.14.14.5

Accepted name: alkanesulfonate monooxygenase

Reaction: an alkanesulfonate + FMNH2 + O2 = an aldehyde + FMN + sulfite + H2O

Glossary: an alkanesulfonate = R-CH2-SO3-
an aldehyde = R-CHO

Other name(s): SsuD; sulfate starvation-induced protein 6; alkanesulfonate,reduced-FMN:oxygen oxidoreductase

Systematic name: alkanesulfonate,FMNH2:oxygen oxidoreductase

Comments: The enzyme from Escherichia coli catalyses the desulfonation of a wide range of aliphatic sulfonates (unsubstituted C1- to C14-sulfonates as well as substituted C2-sulfonates). Does not desulfonate taurine (2-aminoethanesulfonate) or aromatic sulfonates. Does not use FMN as a bound cofactor. Instead, it uses reduced FMN (i.e., FMNH2) as a substrate. FMNH2 is provided by SsuE, the associated FMN reductase (EC 1.5.1.29).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 256383-67-2

References:

1. Eichhorn, E., van der Ploeg, J.R. and Leisinger, T. Characterization of a two-component alkanesulfonate monooxygenase from Escherichia coli. J. Biol. Chem. 274 (1999) 26639-26646. [PMID: 10480865]

[EC 1.14.14.5 created 2002]

[EC 1.14.14.6 Transferred entry: methanesulfonate monooxygenase. Now EC 1.14.13.111, methanesulfonate monooxygenase. Formerly thought to involve FMNH2 but now shown to use NADH. (EC 1.14.14.6 created 2009, deleted 2010)]

[EC 1.14.14.7 Transferred entry: tryptophan 7-halogenase. As oxygen is completely reduced to H2O and is not incorporated into the donor chloride, the enzyme has been transferred to EC 1.14.19.9, tryptophan 7-halogenase (EC 1.14.14.7 created 2009, deleted 2014)]

EC 1.14.14.8

Accepted name: anthranilate 3-monooxygenase (FAD)

Reaction: anthranilate + FADH2 + O2 = 3-hydroxyanthranilate + FAD + H2O

Glossary: anthranilate = 2-aminobenzoate

Other name(s): anthranilate 3-hydroxylase; anthranilate hydroxylase

Systematic name: anthranilate,FADH2:oxygen oxidoreductase (3-hydroxylating)

Comments: This enzyme, isolated from the bacterium Geobacillus thermodenitrificans, participates in the pathway of tryptophan degradation. The enzyme is part of a system that also includes a bifunctional riboflavin kinase/FMN adenylyltransferase and an FAD reductase, which ensures ample supply of FAD to the monooxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Liu, X., Dong, Y., Li, X., Ren, Y., Li, Y., Wang, W., Wang, L. and Feng, L. Characterization of the anthranilate degradation pathway in Geobacillus thermodenitrificans NG80-2. Microbiology 156 (2010) 589-595. [PMID: 19942660]

[EC 1.14.14.8 created 2010]

EC 1.14.14.9

Accepted name: 4-hydroxyphenylacetate 3-monooxygenase

Reaction: 4-hydroxyphenylacetate + FADH2 + O2 = 3,4-dihydroxyphenylacetate + FAD + H2O

Other name(s): p-hydroxyphenylacetate 3-hydroxylase; 4-hydroxyphenylacetic acid-3-hydroxylase; p-hydroxyphenylacetate hydroxylase (FAD); 4 HPA 3-hydroxylase; p-hydroxyphenylacetate 3-hydroxylase (FAD); HpaB

Systematic name: 4-hydroxyphenylacetate,FADH2:oxygen oxidoreductase (3-hydroxylating)

Comments: The enzyme from Escherichia coli attacks a broad spectrum of phenolic compounds. The enzyme uses FADH2 as a substrate rather than a cofactor [4]. FADH2 is provided by EC 1.5.1.36, flavin reductase (NADH) [5,6].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 37256-71-6

References:

1. Adachi, K., Takeda, Y., Senoh, S. and Kita, H. Metabolism of p-hydroxyphenylacetic acid in Pseudomonas ovalis. Biochim. Biophys. Acta 93 (1964) 483-493. [PMID: 14263147]

2. Prieto, M.A., Perez-Aranda, A. and Garcia, J.L. Characterization of an Escherichia coli aromatic hydroxylase with a broad substrate range. J. Bacteriol. 175 (1993) 2162-2167. [PMID: 8458860]

3. Prieto, M.A. and Garcia, J.L. Molecular characterization of 4-hydroxyphenylacetate 3-hydroxylase of Escherichia coli. A two-protein component enzyme. J. Biol. Chem. 269 (1994) 22823-22829. [PMID: 8077235]

4. Xun, L. and Sandvik, E.R. Characterization of 4-hydroxyphenylacetate 3-hydroxylase (HpaB) of Escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase. Appl. Environ. Microbiol. 66 (2000) 481-486. [PMID: 10653707]

5. Galan, B., Diaz, E., Prieto, M.A. and Garcia, J.L. Functional analysis of the small component of the 4-hydroxyphenylacetate 3-monooxygenase of Escherichia coli W: a prototype of a new Flavin:NAD(P)H reductase subfamily. J. Bacteriol. 182 (2000) 627-636. [PMID: 10633095]

6. Louie, T.M., Xie, X.S. and Xun, L. Coordinated production and utilization of FADH2 by NAD(P)H-flavin oxidoreductase and 4-hydroxyphenylacetate 3-monooxygenase. Biochemistry 42 (2003) 7509-7517. [PMID: 12809507]

[EC 1.14.14.9 created 1972 as EC 1.14.13.3, transferred 2011 to EC 1.14.14.9]

EC 1.14.14.10

Accepted name: nitrilotriacetate monooxygenase

Reaction: nitrilotriacetate + FMNH2 + H+ + O2 = iminodiacetate + glyoxylate + FMN + H2O

Systematic name: nitrilotriacetate,FMNH2:oxygen oxidoreductase (glyoxylate-forming)

Comments: Requires Mg2+. The enzyme from Aminobacter aminovorans (previously Chelatobacter heintzii) is part of a two component system that also includes EC 1.5.1.42 (FMN reductase), which provides reduced flavin mononucleotide for this enzyme.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, UM-BBD, CAS registry number:

References:

1. Uetz, T., Schneider, R., Snozzi, M. and Egli, T. Purification and characterization of a two-component monooxygenase that hydroxylates nitrilotriacetate from "Chelatobacter" strain ATCC 29600. J. Bacteriol. 174 (1992) 1179-1188. [PMID: 1735711]

2. Knobel, H.R., Egli, T. and van der Meer, J.R. Cloning and characterization of the genes encoding nitrilotriacetate monooxygenase of Chelatobacter heintzii ATCC 29600. J. Bacteriol. 178 (1996) 6123-6132. [PMID: 8892809]

3. Xu, Y., Mortimer, M.W., Fisher, T.S., Kahn, M.L., Brockman, F.J. and Xun, L. Cloning, sequencing, and analysis of a gene cluster from Chelatobacter heintzii ATCC 29600 encoding nitrilotriacetate monooxygenase and NADH:flavin mononucleotide oxidoreductase. J. Bacteriol. 179 (1997) 1112-1116. [PMID: 9023192]

[EC 1.14.14.10 created 2011]

EC 1.14.14.11

Accepted name: styrene monooxygenase

Reaction: styrene + FADH2 + O2 = (S)-2-phenyloxirane + FAD + H2O

Other name(s): StyA; SMO; NSMOA

Systematic name: styrene,FADH2:oxygen oxidoreductase

Comments: The enzyme catalyses the first step in the aerobic styrene degradation pathway. It forms a two-component system with a reductase (StyB) that utilizes NADH to reduce flavin-adenine dinucleotide, which is then transferred to the oxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Otto, K., Hofstetter, K., Rothlisberger, M., Witholt, B. and Schmid, A. Biochemical characterization of StyAB from Pseudomonas sp. strain VLB120 as a two-component flavin-diffusible monooxygenase. J. Bacteriol. 186 (2004) 5292-5302. [PMID: 15292130]

2. Tischler, D., Kermer, R., Groning, J.A., Kaschabek, S.R., van Berkel, W.J. and Schlomann, M. StyA1 and StyA2B from Rhodococcus opacus 1CP: a multifunctional styrene monooxygenase system. J. Bacteriol. 192 (2010) 5220-5227. [PMID: 20675468]

[EC 1.14.14.11 created 2011]

EC 1.14.14.12

Accepted name: 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione monooxygenase

Reaction: 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + FMNH2 + O2 = 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione + FMN + H2O

Other name(s): HsaA

Systematic name: 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione,FMNH2:oxygen oxidoreductase

Comments: This bacterial enzyme participates in the degradation of several steroids, including cholesterol and testosterone. It can use either FADH or FMNH2 as flavin cofactor. The enzyme forms a two-component system with a reductase (HsaB) that utilizes NADH to reduce the flavin, which is then transferred to the oxygenase subunit.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number:

References:

1. Dresen, C., Lin, L.Y., D'Angelo, I., Tocheva, E.I., Strynadka, N. and Eltis, L.D. A flavin-dependent monooxygenase from Mycobacterium tuberculosis involved in cholesterol catabolism. J. Biol. Chem. 285 (2010) 22264-22275. [PMID: 20448045]

[EC 1.14.14.12 created 2011]

EC 1.14.14.13

Accepted name: 4-(L-γ-glutamylamino)butanoyl-[BtrI acyl-carrier protein] monooxygenase

Reaction: 4-(L-γ-glutamylamino)butanoyl-[BtrI acyl-carrier protein] + FMNH2 + O2 = 4-(L-γ-glutamylamino)-(2S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] + FMN + H2O

Other name(s): btrO (gene name); 4-(L-γ-glutamylamino)butanoyl-[BtrI acyl-carrier protein],FMNH:oxygen oxidoreductase (2-hydroxylating)

Systematic name: 4-(L-γ-glutamylamino)butanoyl-[BtrI acyl-carrier protein],FMNH2:oxygen oxidoreductase (2-hydroxylating)

Comments: Catalyses a step in the biosynthesis of the side chain of the aminoglycoside antibiotics of the butirosin family. FMNH2 is used as a free cofactor. Forms a complex with a dedicated NAD(P)H:FMN oxidoreductase. The enzyme is not able to hydroxylate free substrates, activation by the acyl-carrier protein is mandatory. Octanoyl-S-[BtrI acyl-carrier protein] is also accepted.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Li, Y., Llewellyn, N.M., Giri, R., Huang, F. and Spencer, J.B. Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway. Chem. Biol. 12 (2005) 665-675. [PMID: 15975512]

[EC 1.14.14.13 created 2012]

EC 1.14.14.14

Accepted name: aromatase

Reaction: (1) testosterone + 3 O2 + 3 [reduced NADPH—hemoprotein reductase] = 17β-estradiol + formate + 4 H2O + 3 [oxidized NADPH—hemoprotein reductase] (overall reaction)
(1a) testosterone + O2 + [reduced NADPH—hemoprotein reductase] = 19-hydroxytestosterone + H2O + [oxidized NADPH—hemoprotein reductase]
(1b) 19-hydroxytestosterone + O2 + [reduced NADPH—hemoprotein reductase] = 19-oxotestosterone + 2 H2O + [oxidized NADPH—hemoprotein reductase]
(1c) 19-oxotestosterone + O2 + [reduced NADPH—hemoprotein reductase] = 17β-estradiol + formate + H2O + [oxidized NADPH—hemoprotein reductase]
(2) androst-4-ene-3,17-dione + 3 O2 + 3 [reduced NADPH—hemoprotein reductase] = estrone + formate + 4 H2O + 3 [oxidized NADPH—hemoprotein reductase] (overall reaction)
(2a) androst-4-ene-3,17-dione + O2 + [reduced NADPH—hemoprotein reductase] = 19-hydroxyandrost-4-ene-3,17-dione + H2O + [oxidized NADPH—hemoprotein reductase]
(2b) 19-hydroxyandrost-4-ene-3,17-dione + O2 + [reduced NADPH—hemoprotein reductase] = 19-oxo-androst-4-ene-3,17-dione + 2 H2O + [oxidized NADPH—hemoprotein reductase]
(2c) 19-oxoandrost-4-ene-3,17-dione + O2 + [reduced NADPH—hemoprotein reductase] = estrone + formate + H2O + [oxidized NADPH—hemoprotein reductase]

Other name(s): CYP19A1 (gene name); estrogen synthetase (incorrect)

Systematic name: testosterone monooxygenase (17β-estradiol-forming)

Comments: A cytochrome P450. The enzyme catalyses three sequential hydroxylations of the androgens androst-4-ene-3,17-dione and testosterone, resulting in their aromatization and forming the estrogens estrone and 17β-estradiol, respectively.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Thompson, E.A., Jr. and Siiteri, P.K. The involvement of human placental microsomal cytochrome P-450 in aromatization. J. Biol. Chem. 249 (1974) 5373-5378. [PMID: 4370479]

2. Fishman, J. and Goto, J. Mechanism of estrogen biosynthesis. Participation of multiple enzyme sites in placental aromatase hydroxylations. J. Biol. Chem. 256 (1981) 4466-4471. [PMID: 7217091]

3. Kellis, J.T., Jr. and Vickery, L.E. Purification and characterization of human placental aromatase cytochrome P-450. J. Biol. Chem. 262 (1987) 4413-4420. [PMID: 3104339]

4. Ghosh, D., Griswold, J., Erman, M. and Pangborn, W. Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature 457 (2009) 219-223. [PMID: 19129847]

[EC 1.14.14.14 created 2013]

EC 1.14.14.15

Accepted name: (3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] monooxygenase

Reaction: (3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] + FADH2 + O2 = (3S)-3-amino-3-(3-chloro-4,5-dihydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2] + FAD + H2O

Other name(s): SgcC

Systematic name: (3S)-3-amino-3-(3-chloro-4-hydroxyphenyl)propanoyl-[peptidyl-carrier protein SgcC2],FADH2:oxygen oxidoreductase (5-hydroxylating)

Comments: The enzyme from the actinobacterium Streptomyces globisporus is involved in the biosynthesis of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety prior to incorporation into the chromoprotein antitumor antibiotic C-1027.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Lin, S., Van Lanen, S.G. and Shen, B. Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. J. Am. Chem. Soc. 130 (2008) 6616-6623. [PMID: 18426211]

[EC 1.14.14.15 created 2014]

EC 1.14.14.16

Accepted name: steroid 21-monooxygenase

Reaction: a C21 steroid + [reduced NADPH—hemoprotein reductase] + O2 = a 21-hydroxy-C21-steroid + [oxidized NADPH—hemoprotein reductase] + H2O

Other name(s): steroid 21-hydroxylase; 21-hydroxylase; P450c21; CYP21A2 (gene name)

Systematic name: steroid,NADPH—hemoprotein reductase:oxygen oxidoreductase (21-hydroxylating)

Comments: A P-450 heme-thiolate protein responsible for the conversion of progesterone and 17α-hydroxyprogesterone to their respective 21-hydroxylated derivatives, 11-deoxycorticosterone and 11-deoxycortisol. Involved in the biosynthesis of the hormones aldosterone and cortisol. The electron donor is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Hayano, M. and Dorfman, R.I. The action of adrenal homogenates on progesterone, 17-hydroxyprogesterone and 21-desoxycortisone. Arch. Biochem. Biophys. 36 (1952) 237-239. [PMID: 14934270]

2. Plager, J.E. and Samuels, L.T. Synthesis of C14-17-hydroxy-11-desoxycorticosterone and 17-hydroxycorticosterone by fractionated extracts of adrenal homogenates. Arch. Biochem. Biophys. 42 (1953) 477-478. [PMID: 13031650]

3. Ryan, K.J. and Engel, L.L. Hydroxylation of steroids at carbon 21. J. Biol. Chem. 225 (1957) 103-114. [PMID: 13416221]

4. Kominami, S., Ochi, H., Kobayashi, Y. and Takemori, S. Studies on the steroid hydroxylation system in adrenal cortex microsomes. Purification and characterization of cytochrome P-450 specific for steroid C-21 hydroxylation. J. Biol. Chem. 255 (1980) 3386-3394. [PMID: 6767716]

5. Martineau, I., Belanger, A., Tchernof, A. and Tremblay, Y. Molecular cloning and expression of guinea pig cytochrome P450c21 cDNA (steroid 21-hydroxylase) isolated from the adrenals. J. Steroid Biochem. Mol. Biol. 86 (2003) 123-132. [PMID: 14568563]

6. Arase, M., Waterman, M.R. and Kagawa, N. Purification and characterization of bovine steroid 21-hydroxylase (P450c21) efficiently expressed in Escherichia coli. Biochem. Biophys. Res. Commun. 344 (2006) 400-405. [PMID: 16597434]

[EC 1.14.14.16 created 1961 as EC 1.99.1.11, transferred 1965 to EC 1.14.1.8, transferred 1972 to EC 1.14.99.10, modified 2013]

EC 1.14.14.17

Accepted name: squalene monooxygenase

Reaction: squalene + [reduced NADPH—hemoprotein reductase] + O2 = (3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Other name(s): squalene epoxidase; squalene-2,3-epoxide cyclase; squalene 2,3-oxidocyclase; squalene hydroxylase; squalene oxydocyclase; squalene-2,3-epoxidase

Systematic name: squalene,NADPH:oxygen oxidoreductase (2,3-epoxidizing)

Comments: A flavoprotein (FAD). This enzyme, together with EC 5.4.99.7 lanosterol synthase, was formerly known as squalene oxidocyclase. The electron donor is EC 1.6.2.4, NADPH—hemoprotein reductase [5,7].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Corey, E.J., Russey, W.E. and Ortiz de Montellano, P.R. 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene. J. Am. Chem. Soc. 88 (1966) 4750-4751. [PMID: 5918046]

2. Tchen, T.T. and Bloch, K. On the conversion of squalene to lanosterol in vitro. J. Biol. Chem. 226 (1957) 921-930. [PMID: 13438881]

3. van Tamelen, E.E., Willett, J.D., Clayton, R.B. and Lord, K.E. Enzymic conversion of squalene 2,3-oxide to lanosterol and cholesterol. J. Am. Chem. Soc. 88 (1966) 4752-4754. [PMID: 5918048]

4. Yamamoto, S. and Bloch, K. Studies on squalene epoxidase of rat liver. J. Biol. Chem. 245 (1970) 1670-1674. [PMID: 5438357]

5. Ono, T. and Bloch, K. Solubilization and partial characterization of rat liver squalene epoxidase. J. Biol. Chem. 250 (1975) 1571-1579. [PMID: 234459]

6. Satoh, T., Horie, M., Watanabe, H., Tsuchiya, Y. and Kamei, T. Enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae. Biol. Pharm. Bull. 16 (1993) 349-352. [PMID: 8358382]

7. Chugh, A., Ray, A. and Gupta, J.B. Squalene epoxidase as hypocholesterolemic drug target revisited. Prog. Lipid Res. 42 (2003) 37-50. [PMID: 12467639]

8. He, F., Zhu, Y., He, M. and Zhang, Y. Molecular cloning and characterization of the gene encoding squalene epoxidase in Panax notoginseng. DNA Seq 19 (2008) 270-273. [PMID: 17852349]

[EC 1.14.14.17 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7, transferred 2011 to EC 1.14.13.132]

EC 1.14.14.18

Accepted name: heme oxygenase (biliverdin-producing)

Reaction: protoheme + 3 [reduced NADPH—hemoprotein reductase] + 3 O2 = biliverdin + Fe2+ + CO + 3 [oxidized NADPH—hemoprotein reductase] + 3 H2O

For diagram of reaction click here or mechanism click here.

Other name(s): ORP33 proteins; haem oxygenase (ambiguous); heme oxygenase (decyclizing) (ambiguous); heme oxidase (ambiguous); haem oxidase (ambiguous); heme oxygenase (ambiguous); heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Systematic name: protoheme,NADPH—hemoprotein reductase:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Comments: This mammalian enzyme participates in the degradation of heme. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that converts the α-carbon to CO. The enzyme requires NAD(P)H and EC 1.6.2.4, NADPH—hemoprotein reductase. cf. EC 1.14.15.20, heme oxygenase (biliverdin-producing, ferredoxin).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9059-22-7

References:

1. Maines, M.D., Ibrahim, N.G. and Kappas, K. Solubilization and partial purification of heme oxygenase from rat liver. J. Biol. Chem. 252 (1977) 5900-5903. [PMID: 18477]

2. Sunderman, F.W., Jr., Downs, J.R., Reid, M.C. and Bibeau, L.M. Gas-chromatographic assay for heme oxygenase activity. Clin. Chem. 28 (1982) 2026-2032. [PMID: 6897023]

3. Yoshida, T., Takahashi, S. and Kikuchi, J. Partial purification and reconstitution of the heme oxygenase system from pig spleen microsomes. J. Biochem. (Tokyo) 75 (1974) 1187-1191. [PMID: 4370250]

4. Noguchi, M., Yoshida, T. and Kikuchi, G. Specific requirement of NADPH-cytochrome c reductase for the microsomal heme oxygenase reaction yielding biliverdin IX α. FEBS Lett. 98 (1979) 281-284. [PMID: 105935]

5. Lad, L., Schuller, D.J., Shimizu, H., Friedman, J., Li, H., Ortiz de Montellano, P.R. and Poulos, T.L. Comparison of the heme-free and-bound crystal structures of human heme oxygenase-1. J. Biol. Chem. 278 (2003) 7834-7843. [PMID: 12500973]

[EC 1.14.14.18 created 1972 as EC 1.14.99.3, modified 2006, transferred 2015 to EC 1.14.14.18, modified 2016]

EC 1.14.14.19

Accepted name: steroid 17α-monooxygenase

Reaction: a C21-steroid + [reduced NADPH—hemoprotein reductase] + O2 = a 17α-hydroxy-C21-steroid + [oxidized NADPH—hemoprotein reductase] + H2O

Other name(s): steroid 17α-hydroxylase; cytochrome P-450 17α; cytochrome P-450 (P-450 17α,lyase); 17α-hydroxylase-C17,20 lyase; CYP17; CYP17A1 (gene name)

Systematic name: steroid,NADPH—hemoprotein reductase:oxygen oxidoreductase (17α-hydroxylating)

Comments: Requires NADPH and EC 1.6.2.4, NADPH—hemoprotein reductase. A microsomal hemeprotein that catalyses two independent reactions at the same active site - the 17α-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis, and the conversion of the 17α-hydroxylated products via a 17,20-lyase reaction to form androstenedione and dehydroepiandrosterone, leading to sex hormone biosynthesis (EC 4.1.2.30, 7α-hydroxyprogesterone aldolase). The ratio of the 17α-hydroxylase and 17,20-lyase activities is an important factor in determining the directions of steroid hormone biosynthesis towards biosynthesis of glucocorticoid or sex hormones.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Lynn, W.S. and Brown, R.H. The conversion of progesterone to androgens by testes. J. Biol. Chem. 232 (1958) 1015-1030. [PMID: 13549484]

2. Yoshida, K.-I., Oshima, H. and Troen, P. Studies of the human testis. XIII. Properties of nicotinamide adenine dinucleotide (reduced form)-linked 17α-hydroxylation. J. Clin. Endocrinol. Metab. 50 (1980) 895-899. [PMID: 6966286]

3. Gilep, A.A., Estabrook, R.W. and Usanov, S.A. Molecular cloning and heterologous expression in E. coli of cytochrome P45017α. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species. Biochemistry (Mosc.) 68 (2003) 86-98. [PMID: 12693981]

4. Kolar, N.W., Swart, A.C., Mason, J.I. and Swart, P. Functional expression and characterisation of human cytochrome P45017α in Pichia pastoris. J. Biotechnol. 129 (2007) 635-644. [PMID: 17386955]

5. Pechurskaya, T.A., Lukashevich, O.P., Gilep, A.A. and Usanov, S.A. Engineering, expression, and purification of "soluble" human cytochrome P45017α and its functional characterization. Biochemistry (Mosc.) 73 (2008) 806-811. [PMID: 18707589]

[EC 1.14.14.19 created 1961 as EC 1.99.1.9, transferred 1965 to EC 1.14.1.7, transferred 1972 to EC 1.14.99.9, modified 2013]

EC 1.14.14.20

Accepted name: phenol 2-monooxygenase (FADH2)

Reaction: phenol + FADH2 + O2 = catechol + FAD + H2O

Other name(s): pheA1 (gene name)

Systematic name: phenol,FADH2:oxygen oxidoreductase (2-hydroxylating)

Comments: The enzyme catalyses the ortho-hydroxylation of simple phenols into the corresponding catechols. It accepts 4-methylphenol, 4-chlorophenol, and 4-fluorophenol [1] as well as 4-nitrophenol, 3-nitrophenol, and resorcinol [3]. The enzyme is part of a two-component system that also includes an NADH-dependent flavin reductase. It is strictly dependent on FADH2 and does not accept FMNH2 [1,3]. cf. EC 1.14.13.7, phenol 2-monooxygenase (NADPH).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Kirchner, U., Westphal, A.H., Muller, R. and van Berkel, W.J. Phenol hydroxylase from Bacillus thermoglucosidasius A7, a two-protein component monooxygenase with a dual role for FAD. J. Biol. Chem. 278 (2003) 47545-47553. [PMID: 12968028]

2. van den Heuvel, R.H., Westphal, A.H., Heck, A.J., Walsh, M.A., Rovida, S., van Berkel, W.J. and Mattevi, A. Structural studies on flavin reductase PheA2 reveal binding of NAD in an unusual folded conformation and support novel mechanism of action. J. Biol. Chem. 279 (2004) 12860-12867. [PMID: 14703520]

3. Saa, L., Jaureguibeitia, A., Largo, E., Llama, M.J. and Serra, J.L. Cloning, purification and characterization of two components of phenol hydroxylase from Rhodococcus erythropolis UPV-1. Appl. Microbiol. Biotechnol. 86 (2010) 201-211. [PMID: 19787347]

[EC 1.14.14.20 created 2016]

EC 1.14.14.21

Accepted name: dibenzothiophene monooxygenase

Reaction: dibenzothiophene + 2 FMNH2 + 2 O2 = dibenzothiophene-5,5-dioxide + 2 FMN + 2 H2O (overall reaction)
(1a) dibenzothiophene + FMNH2 + O2 = dibenzothiophene-5-oxide + FMN + H2O
(1b) dibenzothiophene-5-oxide + FMNH2 + O2 = dibenzothiophene-5,5-dioxide + FMN + H2O

Glossary: dibenzothiophene-5,5-dioxide = dibenzothiophene sulfone

Other name(s): dszC (gene name)

Systematic name: dibenzothiophene,FMNH2:oxygen oxidoreductase

Comments: This bacterial enzyme catalyses the first two steps in the desulfurization pathway of dibenzothiophenes, the oxidation of dibenzothiophene into dibenzothiophene sulfone via dibenzothiophene-5-oxide. The enzyme forms a two-component system with a dedicated NADH-dependent FMN reductase (EC 1.5.1.42) encoded by the dszD gene, which also interacts with EC 1.14.14.22, dibenzothiophene sulfone monooxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gray, K.A., Pogrebinsky, O.S., Mrachko, G.T., Xi, L., Monticello, D.J. and Squires, C.H. Molecular mechanisms of biocatalytic desulfurization of fossil fuels. Nat. Biotechnol. 14 (1996) 1705-1709. [PMID: 9634856]

2. Liu, S., Zhang, C., Su, T., Wei, T., Zhu, D., Wang, K., Huang, Y., Dong, Y., Yin, K., Xu, S., Xu, P. and Gu, L. Crystal structure of DszC from Rhodococcus sp. XP at 1.79 Å. Proteins 82 (2014) 1708-1720. [PMID: 24470304]

3. Guan, L.J., Lee, W.C., Wang, S., Ohshiro, T., Izumi, Y., Ohtsuka, J. and Tanokura, M. Crystal structures of apo-DszC and FMN-bound DszC from Rhodococcus erythropolis D-1. FEBS J. 282 (2015) 3126-3135. [PMID: 25627402]

[EC 1.14.14.21 created 2016]

EC 1.14.14.22

Accepted name: dibenzothiophene sulfone monooxygenase

Reaction: dibenzothiophene-5,5-dioxide + 2 FMNH2 + O2 = 2'-hydroxybiphenyl-2-sulfinate + 2 FMN + H2O

Glossary: dibenzothiophene-5,5-dioxide = dibenzothiophene sulfone

Other name(s): dszA (gene name)

Systematic name: dibenzothiophene-5,5-dioxide,FMNH2:oxygen oxidoreductase

Comments: This bacterial enzyme catalyses a step in the desulfurization pathway of dibenzothiophenes. The enzyme forms a two-component system with a dedicated NADH-dependent FMN reductase (EC 1.5.1.42) encoded by the dszD gene, which also interacts with EC 1.14.14.21, dibenzothiophene monooxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gray, K.A., Pogrebinsky, O.S., Mrachko, G.T., Xi, L., Monticello, D.J. and Squires, C.H. Molecular mechanisms of biocatalytic desulfurization of fossil fuels. Nat. Biotechnol. 14 (1996) 1705-1709. [PMID: 9634856]

2. Ohshiro, T., Kojima, T., Torii, K., Kawasoe, H. and Izumi, Y. Purification and characterization of dibenzothiophene (DBT) sulfone monooxygenase, an enzyme involved in DBT desulfurization, from Rhodococcus erythropolis D-1. J. Biosci. Bioeng. 88 (1999) 610-616. [PMID: 16232672]

3. Konishi, J., Ishii, Y., Onaka, T., Ohta, Y., Suzuki, M. and Maruhashi, K. Purification and characterization of dibenzothiophene sulfone monooxygenase and FMN-dependent NADH oxidoreductase from the thermophilic bacterium Paenibacillus sp. strain A11-2. J. Biosci. Bioeng. 90 (2000) 607-613. [PMID: 16232919]

4. Ohshiro, T., Ishii, Y., Matsubara, T., Ueda, K., Izumi, Y., Kino, K. and Kirimura, K. Dibenzothiophene desulfurizing enzymes from moderately thermophilic bacterium Bacillus subtilis WU-S2B: purification, characterization and overexpression. J. Biosci. Bioeng. 100 (2005) 266-273. [PMID: 16243275]

[EC 1.14.14.22 created 2016]

EC 1.14.14.23

Accepted name: cholesterol 7α-monooxygenase

Reaction: cholesterol + [reduced NADPH—hemoprotein reductase] + O2 = 7α-hydroxycholesterol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Other name(s): cholesterol 7α-hydroxylase; CYP7A1 (gene name)

Systematic name: cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (7α-hydroxylating)

Comments: A P-450 heme-thiolate liver protein that catalyses the first step in the biosynthesis of bile acids. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mitton, J.R., Scholan, N.A. and Boyd, G.S. The oxidation of cholesterol in rat liver sub-cellular particles. The cholesterol-7α-hydroxylase enzyme system. Eur. J. Biochem. 20 (1971) 569-579. [PMID: 4397276]

2. Boyd, G.S., Grimwade, A.M. and Lawson, M.E. Studies on rat-liver microsomal cholesterol 7α-hydroxylase. Eur. J. Biochem. 37 (1973) 334-340. [PMID: 4147676]

3. Ogishima, T., Deguchi, S. and Okuda, K. Purification and characterization of cholesterol 7α-hydroxylase from rat liver microsomes. J. Biol. Chem. 262 (1987) 7646-7650. [PMID: 3584134]

4. Nguyen, L.B., Shefer, S., Salen, G., Ness, G., Tanaka, R.D., Packin, V., Thomas, P., Shore, V. and Batta, A. Purification of cholesterol 7 α-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies. J. Biol. Chem. 265 (1990) 4541-4546. [PMID: 2106520]

5. Nguyen, L.B., Shefer, S., Salen, G., Chiang, J.Y. and Patel, M. Cholesterol 7α-hydroxylase activities from human and rat liver are modulated in vitro posttranslationally by phosphorylation/dephosphorylation. Hepatology 24 (1996) 1468-1474. [PMID: 8938182]

[EC 1.14.14.23 created 1976 as EC 1.14.13.17, transferred 2016 to EC 1.14.14.23]

EC 1.14.14.24

Accepted name: vitamin D 25-hydroxylase

Reaction: calciol + O2 + [reduced NADPH—hemoprotein reductase] = calcidiol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: calciol = cholecalciferol = vitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol
calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol

Other name(s): vitamin D2 25-hydroxylase; vitamin D3 25-hydroxylase; CYP2R1

Systematic name: calciol,NADPH—hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)

Comments: A microsomal enzyme isolated from human and mouse liver that bioactivates vitamin D3. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo [4]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Cheng, J.B., Motola, D.L., Mangelsdorf, D.J. and Russell, D.W. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J. Biol. Chem. 278 (2003) 38084-38093. [PMID: 12867411]

2. Shinkyo, R., Sakaki, T., Kamakura, M., Ohta, M. and Inouye, K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem. Biophys. Res. Commun. 324 (2004) 451-457. [PMID: 15465040]

3. Strushkevich, N., Usanov, S.A., Plotnikov, A.N., Jones, G. and Park, H.W. Structural analysis of CYP2R1 in complex with vitamin D3. J. Mol. Biol. 380 (2008) 95-106. [PMID: 18511070]

4. Zhu, J. and Deluca, H.F. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet ? Arch. Biochem. Biophys. 523 (2012) 30-36 . [PMID: 22310641]

[EC 1.14.14.24 created 2012 as EC 1.14.13.159, transferred 2016 to EC 1.14.14.24]

EC 1.14.14.25

Accepted name: cholesterol 24-hydroxylase

Reaction: cholesterol + [reduced NADPH—hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3β,24-diol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: cholesterol = cholest-5-en-3β-ol
(24S)-24-hydroxycholesterol = (24S)-cholest-5-ene-3β,24-diol

Other name(s): cholesterol 24-monooxygenase; CYP46; CYP46A1; cholesterol 24S-hydroxylase; cytochrome P450 46A1

Systematic name: cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)

Comments: A P-450 heme-thiolate protein. The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol [2]. This reaction is the first step in the enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood—brain barrier whereas cholesterol cannot [3]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase [3].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Lund, E.G., Guileyardo, J.M. and Russell, D.W. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc. Natl. Acad. Sci. USA 96 (1999) 7238-7243. [PMID: 10377398]

2. Bogdanovic, N., Bretillon, L., Lund, E.G., Diczfalusy, U., Lannfelt, L., Winblad, B., Russell, D.W. and Björkhem, I. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci. Lett. 314 (2001) 45-48. [PMID: 11698143]

3. Mast, N., Norcross, R., Andersson, U., Shou, M., Nakayama, K., Bjorkhem, I. and Pikuleva, I.A. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry 42 (2003) 14284-14292. [PMID: 14640697]

4. Lund, E.G., Xie, C., Kotti, T., Turley, S.D., Dietschy, J.M. and Russell, D.W. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J. Biol. Chem. 278 (2003) 22980-22988. [PMID: 12686551]

5. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

[EC 1.14.14.25 created 2005 as EC 1.14.13.98, transferred 2016 to EC 1.14.14.25]

EC 1.14.14.26

Accepted name: 24-hydroxycholesterol 7α-hydroxylase

Reaction: (24S)-cholest-5-ene-3β,24-diol + [reduced NADPH—hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3β,7α,24-triol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: (24S)-cholest-5-ene-3β,24-diol = (24S)-24-hydroxycholesterol

Other name(s): 24-hydroxycholesterol 7α-monooxygenase; CYP39A1; CYP39A1 oxysterol 7α-hydroxylase

Systematic name: (24S)-cholest-5-ene-3β,24-diol,NADPH—hemoprotein reductase:oxygen oxidoreductase (7α-hydroxylating)

Comments: A P450 heme-thiolate protein that is found in liver microsomes and in ciliary non-pigmented epithelium [2]. The enzyme is specific for (24S)-cholest-5-ene-3β,24-diol, which is formed mostly in the brain by EC 1.14.14.25, cholesterol 24-hydroxylase. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Li-Hawkins, J., Lund, E.G., Bronson, A.D. and Russell, D.W. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem. 275 (2000) 16543-16549. [PMID: 10748047]

2. Ikeda, H., Ueda, M., Ikeda, M., Kobayashi, H. and Honda, Y. Oxysterol 7alpha-hydroxylase (CYP39A1) in the ciliary nonpigmented epithelium of bovine eye. Lab. Invest. 83 (2003) 349-355. [PMID: 12649335]

3. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

[EC 1.14.14.26 created 2005 as EC 1.14.13.99, transferred 2016 to EC 1.14.14.26]

EC 1.14.14.27

Accepted name: resorcinol 4-hydroxylase (FADH2)

Reaction: resorcinol + FADH2 + O2 = hydroxyquinol + FAD + H2O

Glossary: resorcinol = 1,3-dihydroxybenzene
hydroxyquinol = 1,2,4-trihydroxybenzene

Other name(s): graA (gene name)

Systematic name: resorcinol,FADH2:oxygen oxidoreductase (4-hydroxylating)

Comments: The enzyme, characterized from the bacterium Rhizobium sp. strain MTP-10005, uses FADH2 as a substrate rather than a cofactor. FADH2 is provided by a dedicated EC 1.5.1.36, flavin reductase (NADH). The enzyme participates in the degradation of γ-resorcylate and resorcinol. cf. EC 1.14.13.220, resorcinol 4-hydroxylase (NADH), and EC 1.14.13.219, resorcinol 4-hydroxylase (NADPH).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Ohta, Y. and Ribbons, D.W. Bacterial metabolism of resorcinylic compounds: purification and properties of orcinol hydroxylase and resorcinol hydroxylase from Pseudomonas putida ORC. Eur. J. Biochem. 61 (1976) 259-269. [PMID: 1280]

2. Yoshida, M., Oikawa, T., Obata, H., Abe, K., Mihara, H. and Esaki, N. Biochemical and genetic analysis of the γ-resorcylate (2,6-dihydroxybenzoate) catabolic pathway in Rhizobium sp. strain MTP-10005: identification and functional analysis of its gene cluster. J. Bacteriol. 189 (2007) 1573-1581. [PMID: 17158677]

[EC 1.14.14.27 created 2016]

EC 1.14.14.28

Accepted name: long-chain alkane monooxygenase

Reaction: a long-chain alkane + FMNH2 + O2 = a long-chain primary alcohol + FMN + H2O

Systematic name: long-chain-alkane,FMNH2:oxygen oxidoreductase

Comments: The enzyme, characterized from the bacterium Geobacillus thermodenitrificans NG80-2, is capable of converting alkanes ranging from C15 to C36 into their corresponding primary alcohols [1,2]. The FMNH2 cofactor is provided by an FMN reductase [3].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Feng, L., Wang, W., Cheng, J., Ren, Y., Zhao, G., Gao, C., Tang, Y., Liu, X., Han, W., Peng, X., Liu, R. and Wang, L. Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir. Proc. Natl. Acad. Sci. USA 104 (2007) 5602-5607. [PMID: 17372208]

2. Li, L., Liu, X., Yang, W., Xu, F., Wang, W., Feng, L., Bartlam, M., Wang, L. and Rao, Z. Crystal structure of long-chain alkane monooxygenase (LadA) in complex with coenzyme FMN: unveiling the long-chain alkane hydroxylase. J. Mol. Biol. 376 (2008) 453-465. [PMID: 18164311]

3. Dong, Y., Yan, J., Du, H., Chen, M., Ma, T. and Feng, L. Engineering of LadA for enhanced hexadecane oxidation using random- and site-directed mutagenesis. Appl. Microbiol. Biotechnol. 94 (2012) 1019-1029. [PMID: 22526792]

[EC 1.14.14.28 created 2016]

EC 1.14.14.29

Accepted name: 25/26-hydroxycholesterol 7α-hydroxylase

Reaction: (1) cholest-5-ene-3β,25-diol + [reduced NADPH—hemoprotein reductase] + O2 = cholest-5-ene-3β,7α,25-triol + [oxidized NADPH—hemoprotein reductase] + H2O
(2) (25R)-cholest-5-ene-3β,26-diol + [reduced NADPH—hemoprotein reductase] + O2 = (25R)-cholest-5-ene-3β,7α,26-triol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Other name(s): 25-hydroxycholesterol 7α-monooxygenase; CYP7B1; CYP7B1 oxysterol 7α-hydroxylase; 27-hydroxycholesterol 7-monooxygenase; 27-hydroxycholesterol 7α-hydroxylase; cholest-5-ene-3β,25-diol,NADPH:oxygen oxidoreductase (7α-hydroxylating); 25-hydroxycholesterol 7α-hydroxylase

Systematic name: cholest-5-ene-3β,25/26-diol,[NADPH—hemoprotein reductase]:oxygen oxidoreductase (7α-hydroxylating)

Comments: A P-450 (heme-thiolate) protein. Unlike EC 1.14.14.26, 24-hydroxycholesterol 7α-monooxygenase, which is specific for its oxysterol substrate, this enzyme can also metabolize the oxysterols 24,25-epoxycholesterol, 22-hydroxycholesterol and 24-hydroxycholesterol, but to a lesser extent [2]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Kumiko, O.M., Budai, K. and Javitt, N.B. Cholesterol and 27-hydroxycholesterol 7α-hydroxylation: evidence for two different enzymes. J. Lipid Res. 34 (1993) 581-588.

2. Toll, A., Wikvall, K., Sudjana-Sugiaman, E., Kondo, K.H. and Björkhem, I. 7α hydroxylation of 25-hydroxycholesterol in liver microsomes. Evidence that the enzyme involved is different from cholesterol 7α-hydroxylase. Eur. J. Biochem. 224 (1994) 309-316. [PMID: 7925343]

3. Li-Hawkins, J., Lund, E.G., Bronson, A.D. and Russell, D.W. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem. 275 (2000) 16543-16549. [PMID: 10748047]

4. Ren, S., Marques, D., Redford, K., Hylemon, P.B., Gil, G., Vlahcevic, Z.R. and Pandak, W.M. Regulation of oxysterol 7α-hydroxylase (CYP7B1) in the rat. Metabolism 52 (2003) 636-642. [PMID: 12759897]

5. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

[EC 1.14.14.29 created 2005 as EC 1.14.13.100, modified 2013 (EC 1.14.13.60 created 1999, incorporated 2013), transferred 2016 to EC 1.14.14.29]

EC 1.14.14.30

Accepted name: isobutylamine N-monooxygenase

Reaction: (1) 2-methylpropan-1-amine + FADH2 + O2 = N-(2-methylpropyl)hydroxylamine + FAD + H2O
(2) 2-methylpropan-1-amine + FMNH2 + O2 = N-(2-methylpropyl)hydroxylamine + FMN + H2O

Glossary: 2-methylpropan-1-amine = isobutylamine
N-(2-methylpropyl)hydroxylamine = N-hydroxy-2-methylpropan-1-amine = isobutylhydroxylamine

Other name(s): vlmH (gene name)

Systematic name: 2-methylpropan-1-amine,FADH2:O2 N-oxidoreductase

Comments: The enzyme, characterized from the bacterium Streptomyces viridifaciens, is part of a two component system that also includes a flavin reductase, which provides reduced flavin mononucleotide for this enzyme. The enzyme, which is involved in the biosynthesis of the azoxy antibiotic valanimycin, has a similar activity with either FMNH2 or FADH2. It exhibits broad specificity, and also accepts propan-1-amine, butan-1-amine, butan-2-amine and benzylamine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Parry, R.J. and Li, W. Purification and characterization of isobutylamine N-hydroxylase from the valanimycin producer Streptomyces viridifaciens MG456-hF10. Arch. Biochem. Biophys. 339 (1997) 47-54. [PMID: 9056232]

2. Parry, R.J., Li, W. and Cooper, H.N. Cloning, analysis, and overexpression of the gene encoding isobutylamine N-hydroxylase from the valanimycin producer, Streptomyces viridifaciens. J. Bacteriol. 179 (1997) 409-416. [PMID: 8990292]

3. Parry, R.J. and Li, W. An NADPH:FAD oxidoreductase from the valanimycin producer, Streptomyces viridifaciens. Cloning, analysis, and overexpression. J. Biol. Chem. 272 (1997) 23303-23311. [PMID: 9287340]

[EC 1.14.14.30 created 2016, modified 2017]

EC 1.14.14.31

Accepted name: ipsdienol synthase

Reaction: myrcene + [reduced NADPH—hemoprotein reductase] + O2 = (R)-ipsdienol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: myrcene = 7-methyl-3-methyleneocta-1,6-diene
ipsdienol = 2-methyl-6-methyleneocta-2,7-dien-4-ol

Other name(s): myrcene hydroxylase; CYP9T2; CYP9T3

Systematic name: myrcene,NADPH—hemoprotein reductase:O2 oxidoreductase (hydroxylating)

Comments: A cytochrome P-450 heme-thiolate protein. Involved in the insect aggregation pheromone production. Isolated from the pine engraver beetle, Ips pini. A small amount of (S)-ipsdienol is also formed. In vitro it also hydroxylated (+)- and (–)-α-pinene, 3-carene, and (+)-limonene, but not α-phellandrene, (–)-β-pinene, γ-terpinene, or terpinolene.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Sandstrom, P., Welch, W.H., Blomquist, G.J. and Tittiger, C. Functional expression of a bark beetle cytochrome P450 that hydroxylates myrcene to ipsdienol. Insect Biochem. Mol. Biol. 36 (2006) 835-845. [PMID: 17046597]

2. Song, M., Kim, A.C., Gorzalski, A.J., MacLean, M., Young, S., Ginzel, M.D., Blomquist, G.J. and Tittiger, C. Functional characterization of myrcene hydroxylases from two geographically distinct Ips pini populations. Insect Biochem. Mol. Biol. 43 (2013) 336-343. [PMID: 23376633]

[EC 1.14.14.31 created 2015 as EC 1.14.13.207, transferred 2016 to EC 1.14.14.31]

EC 1.14.14.32

Accepted name: 17α-hydroxyprogesterone deacetylase

Reaction: (1) 17α-hydroxyprogesterone + [reduced NADPH—hemoprotein reductase] + O2 = androstenedione + acetate + [oxidized NADPH—hemoprotein reductase] + H2O
(2) 17α-hydroxypregnenolone + [reduced NADPH—hemoprotein reductase] + O2 = 3β-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH—hemoprotein reductase] + H2

Glossary: androstenedione = androst-4-ene-3,17-dione

Other name(s): C-17/C-20 lyase; 17α-hydroxyprogesterone acetaldehyde-lyase; CYP17; CYP17A1 (gene name); 17α-hydroxyprogesterone 17,20-lyase

Systematic name: 17α-hydroxyprogesterone,NADPH—hemoprotein reductase:oxygen oxidoreductase (17α-hydroxylating, acetate-releasing)

Comments: A microsomal cytochrome P-450 (heme-thiolate) protein that catalyses two independent reactions at the same active site - the 17-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis (EC 1.14.14.19), and the conversion of the 17-hydroxylated products via a 17,20-lyase reaction to form androstenedione and 3β-hydroxyandrost-5-en-17-one, leading to sex hormone biosynthesis. The activity of this reaction is dependent on the allosteric interaction of the enzyme with cytochrome b5 without any transfer of electrons from the cytochrome [2,4]. The enzymes from different organisms differ in their substrate specificity. While the enzymes from pig, hamster, and rat accept both 17α-hydroxyprogesterone and 17α-hydroxypregnenolone, the enzymes from human, bovine, sheep, goat, and bison do not accept the former, and the enzyme from guinea pig does not accept the latter [1].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gilep, A.A., Estabrook, R.W. and Usanov, S.A. Molecular cloning and heterologous expression in E. coli of cytochrome P45017α. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species. Biochemistry (Mosc.) 68 (2003) 86-98. [PMID: 12693981]

2. Auchus, R.J., Lee, T.C. and Miller, W.L. Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer. J. Biol. Chem. 273 (1998) 3158-3165. [PMID: 9452426]

3. Mak, P.J., Gregory, M.C., Denisov, I.G., Sligar, S.G. and Kincaid, J.R. Unveiling the crucial intermediates in androgen production. Proc. Natl. Acad. Sci. USA 112 (2015) 15856-15861. [PMID: 26668369]

4. Simonov, A.N., Holien, J.K., Yeung, J.C., Nguyen, A.D., Corbin, C.J., Zheng, J., Kuznetsov, V.L., Auchus, R.J., Conley, A.J., Bond, A.M., Parker, M.W., Rodgers, R.J. and Martin, L.L. Mechanistic scrutiny identifies a kinetic role for cytochrome b5 regulation of human cytochrome P450c17 (CYP17A1, P450 17A1). PLoS One 10 (2015) e0141252. [PMID: 26587646]

5. Bhatt, M.R., Khatri, Y., Rodgers, R.J. and Martin, L.L. Role of cytochrome b5 in the modulation of the enzymatic activities of cytochrome P450 17α-hydroxylase/17,20-lyase (P450 17A1). J. Steroid Biochem. Mol. Biol. (2016) . [PMID: 26976652]

[EC 1.14.14.32 created 1976 as EC 4.1.2.30, transferred 2016 to EC 1.14.14.32]

EC 1.14.14.33

Accepted name: ethylenediaminetetraacetate monooxygenase

Reaction: ethylenediaminetetraacetate + 2 FMNH2 + 2 O2 = ethylenediamine-N,N'-diacetate + 2 glyoxylate + 2 FMN + 2 H2O (overall reaction)
(1a) ethylenediaminetetraacetate + FMNH2 + O2 = ethylenediaminetriacetate + glyoxylate + FMN + H2O
(1b) ethylenediaminetriacetate + FMNH2 + O2 = ethylenediamine-N,N'-diacetate + glyoxylate + FMN + H2O

Glossary: ethylenediaminetetraacetate = EDTA

Systematic name: ethylenediaminetetraacetate,FMNH2:O2 oxidoreductase (glyoxylate-forming)

Comments: The enzyme is part of a two component system that also includes EC 1.5.1.42, FMN reductase (NADH), which provides reduced flavin mononucleotide for this enzyme. It acts on EDTA only when it is complexed with divalent cations such as Mg2+, Zn2+, Mn2+, Co2+, or Cu2+. While the enzyme has a substrate overlap with EC 1.14.14.10, nitrilotriacetate monooxygenase, it has a much wider substrate range, which includes nitrilotriacetate (NTA) and diethylenetriaminepentaacetate (DTPA) in addition to EDTA.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Witschel, M., Nagel, S. and Egli, T. Identification and characterization of the two-enzyme system catalyzing oxidation of EDTA in the EDTA-degrading bacterial strain DSM 9103. J. Bacteriol. 179 (1997) 6937-6943. [PMID: 9371437]

2. Payne, J.W., Bolton, H., Jr., Campbell, J.A. and Xun, L. Purification and characterization of EDTA monooxygenase from the EDTA-degrading bacterium BNC1. J. Bacteriol. 180 (1998) 3823-3827. [PMID: 9683478]

3. Bohuslavek, J., Payne, J.W., Liu, Y., Bolton, H., Jr. and Xun, L. Cloning, sequencing, and characterization of a gene cluster involved in EDTA degradation from the bacterium BNC1. Appl. Environ. Microbiol. 67 (2001) 688-695. [PMID: 11157232]

[EC 1.14.14.33 created 2016]

EC 1.14.14.34

Accepted name: methanesulfonate monooxygenase (FMNH2)

Reaction: methanesulfonate + FMNH2 + O2 = formaldehyde + FMN + sulfite + H2O

Glossary: methanesulfonate = CH3-SO3-
formaldehyde = H-CHO

Other name(s): msuD (gene name); ssuD (gene name)

Systematic name: methanesulfonate,FMNH2:oxygen oxidoreductase

Comments: The enzyme, characterized from Pseudomonas strains, allows the organisms to utilize methanesulfonate as their sulfur source. It acts in combination with a dedicated NADH-dependent FMN reductase (EC 1.5.1.42), which provides it with reduced FMN. cf. EC 1.14.13.111, methanesulfonate monooxygenase (NADH).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Kertesz, M.A., Schmidt-Larbig, K. and Wuest, T. A novel reduced flavin mononucleotide-dependent methanesulfonate sulfonatase encoded by the sulfur-regulated msu operon of Pseudomonas aeruginosa. J. Bacteriol. 181 (1999) 1464-1473. [PMID: 10049377]

2. Endoh, T., Kasuga, K., Horinouchi, M., Yoshida, T., Habe, H., Nojiri, H. and Omori, T. Characterization and identification of genes essential for dimethyl sulfide utilization in Pseudomonas putida strain DS1. Appl. Microbiol. Biotechnol. 62 (2003) 83-91. [PMID: 12835925]

[EC 1.14.14.34 created 2016]

EC 1.14.14.35

Accepted name: dimethylsulfone monooxygenase

Reaction: dimethyl sulfone + FMNH2 + O2 = methanesulfinate + formaldehyde + FMN + H2O

Other name(s): sfnG (gene name)

Systematic name: dimethyl sulfone,FMNH2:oxygen oxidoreductase

Comments: The enzyme, characterized from Pseudomonas spp., is involved in a dimethyl sulfide degradation pathway. It is dependent on NAD(P)H-dependent FMN reductase (EC 1.5.1.38, EC 1.5.1.39, or EC 1.5.1.42), which provides it with reduced FMN. The product, methanesulfinate, is oxidized spontaneously to methanesulfonate in the presence of dioxygen and FMNH2.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Endoh, T., Habe, H., Nojiri, H., Yamane, H. and Omori, T. The σ54-dependent transcriptional activator SfnR regulates the expression of the Pseudomonas putida sfnFG operon responsible for dimethyl sulphone utilization. Mol. Microbiol. 55 (2005) 897-911. [PMID: 15661012]

2. Wicht, D.K. The reduced flavin-dependent monooxygenase SfnG converts dimethylsulfone to methanesulfinate. Arch. Biochem. Biophys. 604 (2016) 159-166. [PMID: 27392454]

[EC 1.14.14.35 created 2016]

EC 1.14.14.36

Accepted name: tyrosine N-monooxygenase

Reaction: L-tyrosine + 2 O2 + 2 [reduced NADPH—hemoprotein reductase] = (E)-[4-hydroxyphenylacetaldehyde oxime] + 2 [oxidized NADPH—hemoprotein reductase] + CO2 + 3 H2O (overall reaction)
(1a) L-tyrosine + O2 + [reduced NADPH—hemoprotein reductase] = N-hydroxy-L-tyrosine + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) N-hydroxy-L-tyrosine + O2 + [reduced NADPH—hemoprotein reductase] = N,N-dihydroxy-L-tyrosine + [oxidized NADPH—hemoprotein reductase] + H2O
(1c) N,N-dihydroxy-L-tyrosine = (E)-[4-hydroxyphenylacetaldehyde oxime] + CO2 + H2O

For diagram of reaction click here.

Other name(s): tyrosine N-hydroxylase; CYP79A1

Systematic name: L-tyrosine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme is involved in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum, along with EC 1.14.14.37, 4-hydroxyphenylacetaldehyde oxime monooxygenase and EC 2.4.1.85, cyanohydrin β-glucosyltransferase. Some 2-(4-hydroxyphenyl)-1-nitroethane is formed as a side product.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Halkier, B.A. and Møller, B.L. The biosynthesis of cyanogenic glucosides in higher plants. Identification of three hydroxylation steps in the biosynthesis of dhurrin in Sorghum bicolor (L.) Moench and the involvement of 1-ACI-nitro-2-(p-hydroxyphenyl)ethane as an intermediate. J. Biol. Chem. 265 (1990) 21114-21121. [PMID: 2250015]

2. Sibbesen, O., Koch, B., Halkier, B.A. and Møller, B.L. Cytochrome P-450TYR is a multifunctional heme-thiolate enzyme catalyzing the conversion of L-tyrosine to p-hydroxyphenylacetaldehyde oxime in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench. J. Biol. Chem. 270 (1995) 3506-3511. [PMID: 7876084]

3. Kahn, R.A., Fahrendorf, T., Halkier, B.A. and Møller, B.L. Substrate specificity of the cytochrome P450 enzymes CYP79A1 and CYP71E1 involved in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench. Arch. Biochem. Biophys. 363 (1999) 9-18. [PMID: 10049494]

4. Bak, S., Olsen, C.E., Halkier, B.A. and Moller, B.L. Transgenic tobacco and Arabidopsis plants expressing the two multifunctional sorghum cytochrome P450 enzymes, CYP79A1 and CYP71E1, are cyanogenic and accumulate metabolites derived from intermediates in Dhurrin biosynthesis. Plant Physiol. 123 (2000) 1437-1448. [PMID: 10938360]

5. Nielsen, J.S. and Møller, B.L. Cloning and expression of cytochrome P450 enzymes catalyzing the conversion of tyrosine to p-hydroxyphenylacetaldoxime in the biosynthesis of cyanogenic glucosides in Triglochin maritima. Plant Physiol. 122 (2000) 1311-1321. [PMID: 10759528]

6. Busk, P.K. and Møller, B.L. Dhurrin synthesis in sorghum is regulated at the transcriptional level and induced by nitrogen fertilization in older plants. Plant Physiol. 129 (2002) 1222-1231. [PMID: 12114576]

7. Kristensen, C., Morant, M., Olsen, C.E., Ekstrøm, C.T., Galbraith, D.W., Møller, B.L. and Bak, S. Metabolic engineering of dhurrin in transgenic Arabidopsis plants with marginal inadvertent effects on the metabolome and transcriptome. Proc. Natl. Acad. Sci. USA 102 (2005) 1779-1784. [PMID: 15665094]

8. Clausen, M., Kannangara, R.M., Olsen, C.E., Blomstedt, C.K., Gleadow, R.M., Jørgensen, K., Bak, S., Motawie, M.S. and Møller, B.L. The bifurcation of the cyanogenic glucoside and glucosinolate biosynthetic pathways. Plant J. 84 (2015) 558-573. [PMID: 26361733]

[EC 1.14.14.36 created 1992 as EC 1.14.13.41, modified 2001, modified 2005, transferred 2016 to EC 1.14.14.36]

EC 1.14.14.37

Accepted name: 4-hydroxyphenylacetaldehyde oxime monooxygenase

Reaction: (E)-4-hydroxyphenylacetaldehyde oxime + [reduced NADPH—hemoprotein reductase] + O2 = (S)-4-hydroxymandelonitrile + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) (E)-4-hydroxyphenylacetaldehyde oxime = (Z)-4-hydroxyphenylacetaldehyde oxime
(1b) (Z)-4-hydroxyphenylacetaldehyde oxime = 4-hydroxyphenylacetonitrile + H2O
(1c) 4-hydroxyphenylacetonitrile + [reduced NADPH—hemoprotein reductase] + O2 = (S)-4-hydroxymandelonitrile + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: (S)-4-hydroxymandelonitrile = (2S)-hydroxy(4-hydroxyphenyl)acetonitrile

Other name(s): 4-hydroxybenzeneacetaldehyde oxime monooxygenase; cytochrome P450II-dependent monooxygenase; NADPH-cytochrome P450 reductase (CYP71E1); CYP71E1; 4-hydroxyphenylacetaldehyde oxime,NADPH:oxygen oxidoreductase

Systematic name: (E)-4-hydroxyphenylacetaldehyde oxime,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments: This cytochrome P-450 (heme thiolate) enzyme is involved in the biosynthesis of the cyanogenic glucoside dhurrin in sorghum. It catalyses three different activities - isomerization of the (E) isomer to the (Z) isomer, dehydration, and C-hydroxylation.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. MacFarlane, I.J., Lees, E.M. and Conn, E.E. The in vitro biosynthesis of dhurrin, the cyanogenic glycoside of Sorghum bicolor. J. Biol. Chem. 250 (1975) 4708-4713. [PMID: 237909]

2. Shimada, M. and Conn, E.E. The enzymatic conversion of p-hydroxyphenylacetaldoxime to p-hydroxymandelonitrile. Arch. Biochem. Biophys. 180 (1977) 199-207. [PMID: 193443]

3. Busk, P.K. and Møller, B.L. Dhurrin synthesis in sorghum is regulated at the transcriptional level and induced by nitrogen fertilization in older plants. Plant Physiol. 129 (2002) 1222-1231. [PMID: 12114576]

4. Kristensen, C., Morant, M., Olsen, C.E., Ekstrøm, C.T., Galbraith, D.W., Møller, B.L. and Bak, S. Metabolic engineering of dhurrin in transgenic Arabidopsis plants with marginal inadvertent effects on the metabolome and transcriptome. Proc. Natl. Acad. Sci. USA 102 (2005) 1779-1784. [PMID: 15665094]

5. Clausen, M., Kannangara, R.M., Olsen, C.E., Blomstedt, C.K., Gleadow, R.M., Jørgensen, K., Bak, S., Motawie, M.S. and Møller, B.L. The bifurcation of the cyanogenic glucoside and glucosinolate biosynthetic pathways. Plant J. 84 (2015) 558-573. [PMID: 26361733]

[EC 1.14.14.37 created 2000 as EC 1.14.13.68, modified 2005, transferred 2016 to EC 1.14.14.37]

EC 1.14.14.38

Accepted name: valine N-monooxygenase

Reaction: L-valine + 2 O2 + 2 [reduced NADPH—hemoprotein reductase] = (E)-2-methylpropanal oxime + 2 [oxidized NADPH—hemoprotein reductase] + CO2 + 3 H2O (overall reaction)
(1a) L-valine + O2 + [reduced NADPH—hemoprotein reductase] = N-hydroxy-L-valine + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) N-hydroxy-L-valine + O2 + [reduced NADPH—hemoprotein reductase] = N,N-dihydroxy-L-valine + [oxidized NADPH—hemoprotein reductase] + H2O
(1c) N,N-dihydroxy-L-valine = (E)-2-methylpropanal oxime + CO2 + H2O

Other name(s): CYP79D1; CYP79D2

Systematic name: L-valine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein. This enzyme catalyses two successive N-hydroxylations of L-valine, the committed step in the biosynthesis of the cyanogenic glucoside linamarin in Manihot esculenta (cassava). The product of the two hydroxylations, N,N-dihydroxy-L-valine, is labile and undergoes dehydration and decarboxylation that produce the (E) isomer of the oxime. It is still not known whether the decarboxylation is spontaneous or catalysed by the enzyme. The enzyme can also accept L-isoleucine as substrate, with a lower activity. It is different from EC 1.14.14.39, isoleucine N-monooxygenase, which prefers L-isoleucine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Andersen, M.D., Busk, P.K., Svendsen, I. and Møller, B.L. Cytochromes P-450 from cassava (Manihot esculenta Crantz) catalyzing the first steps in the biosynthesis of the cyanogenic glucosides linamarin and lotaustralin. Cloning, functional expression in Pichia pastoris, and substrate specificity of the isolated recombinant enzymes. J. Biol. Chem. 275 (2000) 1966-1975. [PMID: 10636899]

2. Forslund, K., Morant, M., Jørgensen, B., Olsen, C.E., Asamizu, E., Sato, S., Tabata, S. and Bak, S. Biosynthesis of the nitrile glucosides rhodiocyanoside A and D and the cyanogenic glucosides lotaustralin and linamarin in Lotus japonicus. Plant Physiol. 135 (2004) 71-84. [PMID: 15122013]

[EC 1.14.14.38 created 2010 as EC 1.14.13.118, transferred 2017 to EC 1.14.14.38]

EC 1.14.14.39

Accepted name: isoleucine N-monooxygenase

Reaction: L-isoleucine + 2 O2 + 2 [reduced NADPH—hemoprotein reductase] = (1E,2S)-2-methylbutanal oxime + 2 [oxidized NADPH—hemoprotein reductase] + CO2 + 3 H2O (overall reaction)
(1a) L-isoleucine + O2 + [reduced NADPH—hemoprotein reductase] = N-hydroxy-L-isoleucine + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) N-hydroxy-L-isoleucine + O2 + [reduced NADPH—hemoprotein reductase] = N,N-dihydroxy-L-isoleucine + [oxidized NADPH—hemoprotein reductase] + H2O
(1c) N,N-dihydroxy-L-isoleucine = (1E,2S)-2-methylbutanal oxime + CO2 + H2O (spontaneous)

Other name(s): CYP79D3 (gene name); CYP79D4 (gene name)

Systematic name: L-isoleucine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments: This cytochrome P-450 (heme-thiolate) enzyme, found in plants, catalyses two successive N-hydroxylations of L-isoleucine, the committed step in the biosynthesis of the cyanogenic glucoside lotaustralin. The product of the two hydroxylations, N,N-dihydroxy-L-isoleucine, is labile and undergoes dehydration followed by decarboxylation, producing the oxime. It is still not known whether the decarboxylation is spontaneous or catalysed by the enzyme. The enzyme can also accept L-valine, but with a lower activity. cf. EC 1.14.14.38, valine N-monooxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Andersen, M.D., Busk, P.K., Svendsen, I. and Møller, B.L. Cytochromes P-450 from cassava (Manihot esculenta Crantz) catalyzing the first steps in the biosynthesis of the cyanogenic glucosides linamarin and lotaustralin. Cloning, functional expression in Pichia pastoris, and substrate specificity of the isolated recombinant enzymes. J. Biol. Chem. 275 (2000) 1966-1975. [PMID: 10636899]

2. Forslund, K., Morant, M., Jørgensen, B., Olsen, C.E., Asamizu, E., Sato, S., Tabata, S. and Bak, S. Biosynthesis of the nitrile glucosides rhodiocyanoside A and D and the cyanogenic glucosides lotaustralin and linamarin in Lotus japonicus. Plant Physiol. 135 (2004) 71-84. [PMID: 15122013]

[EC 1.14.14.39 created 2010 as EC 1.14.13.117, transferred 2017 to EC 1.14.14.39]

EC 1.14.14.40

Accepted name: phenylalanine N-monooxygenase

Reaction: L-phenylalanine + 2 O2 + 2 [reduced NADPH—hemoprotein reductase] = (E)-phenylacetaldoxime + 2 [oxidized NADPH—hemoprotein reductase] + CO2 + 3 H2O (overall reaction)
(1a) L-phenylalanine + O2 + [reduced NADPH—hemoprotein reductase] = N-hydroxy-L-phenylalanine + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) N-hydroxy-L-phenylalanine + O2 + [reduced NADPH—hemoprotein reductase] = N,N-dihydroxy-L-phenylalanine + [oxidized NADPH—hemoprotein reductase] + H2O
(1c) N,N-dihydroxy-L-phenylalanine = (E)-phenylacetaldoxime + CO2 + H2O

Other name(s): phenylalanine N-hydroxylase; CYP79A2 (gene name); CYP79D16 (gene name)

Systematic name: L-phenylalanine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments: This cytochrome P-450 (heme-thiolate) enzyme, found in plants, catalyses two successive N-hydroxylations of L-phenylalanine, a committed step in the biosynthesis of benzylglucosinolate and the cyanogenic glucosides (R)-prunasin and (R)-amygdalin. The product of the two hydroxylations, N,N-dihydroxy-L-phenylalanine, is labile and undergoes dehydration followed by decarboxylation, producing an oxime. It is still not known whether the decarboxylation is spontaneous or catalysed by the enzyme.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Wittstock, U. and Halkier, B.A. Cytochrome P450 CYP79A2 from Arabidopsis thaliana L. Catalyzes the conversion of L-phenylalanine to phenylacetaldoxime in the biosynthesis of benzylglucosinolate. J. Biol. Chem. 275 (2000) 14659-14666. [PMID: 10799553]

2. Yamaguchi, T., Yamamoto, K. and Asano, Y. Identification and characterization of CYP79D16 and CYP71AN24 catalyzing the first and second steps in L-phenylalanine-derived cyanogenic glycoside biosynthesis in the Japanese apricot, Prunus mume Sieb. et Zucc. Plant Mol. Biol. 86 (2014) 215-223. [PMID: 25015725]

[EC 1.14.14.40 created 2011 as EC 1.14.13.124, transferred 2017 to EC 1.14.14.40]

EC 1.14.14.41

Accepted name: (E)-2-methylbutanal oxime monooxygenase

Reaction: (1) (E)-2-methylbutanal oxime + [reduced NADPH—hemoprotein reductase] + O2 = 2-hydroxy-2-methylbutanenitrile + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) (E)-2-methylbutanal oxime = (Z)-2-methylbutanal oxime
(1b) (Z)-2-methylbutanal oxime = 2-methylbutanenitrile + H2O
(1c) 2-methylbutanenitrile + [reduced NADPH—hemoprotein reductase] + O2 = 2-hydroxy-2-methylbutanenitrile + [oxidized NADPH—hemoprotein reductase] + H2O
(2) (E)-2-methylpropanal oxime + [reduced NADPH—hemoprotein reductase] + O2 = 2-hydroxy-2-methylpropanenitrile + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(2a) (E)-2-methylpropanal oxime = (Z)-2-methylpropanal oxime
(2b) (Z)-2-methylpropanal oxime = 2-methylpropanenitrile + H2O
(2c) 2-methylpropanenitrile + [reduced NADPH—hemoprotein reductase] + O2 = 2-hydroxy-2-methylpropanenitrile + [oxidized NADPH—hemoprotein reductase] + H2O

Other name(s): CYP71E7 (gene name)

Systematic name: (E)-2-methylbutanal oxime,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments: This cytochrome P-450 (heme thiolate) enzyme is involved in the biosynthesis of the cyanogenic glucosides lotaustralin and linamarin. It catalyses three different activities - isomerization of its substrate, the (E) isomer, to the (Z) isomer, dehydration, and C-hydroxylation.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Jørgensen, K., Morant, A.V., Morant, M., Jensen, N.B., Olsen, C.E., Kannangara, R., Motawia, M.S., Møller, B.L. and Bak, S. Biosynthesis of the cyanogenic glucosides linamarin and lotaustralin in cassava: isolation, biochemical characterization, and expression pattern of CYP71E7, the oxime-metabolizing cytochrome P450 enzyme. Plant Physiol. 155 (2011) 282-292. [PMID: 21045121]

[EC 1.14.14.41 created 2017]

EC 1.14.14.42

Accepted name: homomethionine N-monooxygenase

Reaction: an L-polyhomomethionine + 2 O2 + 2 [reduced NADPH—hemoprotein reductase] = an ω-(methylthio)-(E)-alkanal oxime + CO2 + 3 H2O + 2 [oxidized NADPH—hemoprotein reductase] (overall reaction)
(1a) an L-polyhomomethionine + O2 + [reduced NADPH—hemoprotein reductase] = an L-N-hydroxypolyhomomethionine + H2O + [oxidized NADPH—hemoprotein reductase]
(1b) an L-N-hydroxypolyhomomethionine + O2 + [reduced NADPH—hemoprotein reductase] = an L-N,N-dihydroxypolyhomomethionine + H2O + [oxidized NADPH—hemoprotein reductase]
(1c) an L-N,N-dihydroxypolyhomomethionine = ω-(methylthio)-(E)-alkanal oxime + CO2 + H2O

Other name(s): CYP79F1 (gene name); CYP79F2 (gene name)

Systematic name: L-homomethionine,[NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments: This plant cytochrome P-450 (heme thiolate) enzyme is involved in methionine-derived aliphatic glucosinolates biosynthesis. It catalyses two successive N-hydroxylations, which are followed by dehydration and decarboxylation. CYP79F1 from Arabidopsis thaliana can metabolize homo-, di-, tri-, tetra-, penta-, and hexahomomethionine to their corresponding aldoximes, while CYP79F2 from the same plant can only metabolize penta- and hexahomomethionine.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Hansen, C.H., Wittstock, U., Olsen, C.E., Hick, A.J., Pickett, J.A. and Halkier, B.A. Cytochrome p450 CYP79F1 from Arabidopsis catalyzes the conversion of dihomomethionine and trihomomethionine to the corresponding aldoximes in the biosynthesis of aliphatic glucosinolates. J. Biol. Chem. 276 (2001) 11078-11085. [PMID: 11133994]

2. Chen, S., Glawischnig, E., Jørgensen, K., Naur, P., Jorgensen, B., Olsen, C.E., Hansen, C.H., Rasmussen, H., Pickett, J.A. and Halkier, B.A. CYP79F1 and CYP79F2 have distinct functions in the biosynthesis of aliphatic glucosinolates in Arabidopsis. Plant J. 33 (2003) 923-937. [PMID: 12609033]

[EC 1.14.14.42 created 2017]

EC 1.14.14.43

Accepted name: (methylthio)alkanaldoxime N-monooxygenase

Reaction: an (E)-ω-(methylthio)alkanal oxime + O2 + glutathione + [reduced NADPH—hemoprotein reductase] = an (E)-1-(glutathione-S-yl)-ω-(methylthio)alkylhydroximate + 2 H2O + [oxidized NADPH—hemoprotein reductase] (overall reaction)
(1a) an (E)-ω-(methylthio)alkanal oxime + O2 + [reduced NADPH—hemoprotein reductase] = a 1-aci-nitro-ω-(methylthio)alkane + H2O + [oxidized NADPH—hemoprotein reductase]
(1b) a 1-aci-nitro-ω-(methylthio)alkane + glutathione = an (E)-1-(glutathione-S-yl)-ω-(methylthio)alkylhydroximate + H2O

Other name(s): CYP83A1 (gene name)

Systematic name: (E)-ω-(methylthio)alkananaldoxime,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (N-hydroxylating)

Comments: This cytochrome P-450 (heme thiolate) enzyme is involved in the biosynthesis of glucosinolates in plants. The enzyme catalyses an N-hydroxylation of the E isomer of n-(methylthio)aldoximes, forming an aci-nitro intermediate that reacts non-enzymically with glutathione to produce an N-alkyl-thiohydroximate adduct, the committed precursor of glucosinolates. In the absence of a thiol compound, the enzyme is suicidal, probably due to interaction of the reactive aci-nitro intermediate with active site residues.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Bak, S., Tax, F.E., Feldmann, K.A., Galbraith, D.W. and Feyereisen, R. CYP83B1, a cytochrome P450 at the metabolic branch point in auxin and indole glucosinolate biosynthesis in Arabidopsis. Plant Cell 13 (2001) 101-111. [PMID: 11158532]

2. Naur, P., Petersen, B.L., Mikkelsen, M.D., Bak, S., Rasmussen, H., Olsen, C.E. and Halkier, B.A. CYP83A1 and CYP83B1, two nonredundant cytochrome P450 enzymes metabolizing oximes in the biosynthesis of glucosinolates in Arabidopsis. Plant Physiol. 133 (2003) 63-72. [PMID: 12970475]

3. Clausen, M., Kannangara, R.M., Olsen, C.E., Blomstedt, C.K., Gleadow, R.M., Jørgensen, K., Bak, S., Motawie, M.S. and Møller, B.L. The bifurcation of the cyanogenic glucoside and glucosinolate biosynthetic pathways. Plant J. 84 (2015) 558-573. [PMID: 26361733]

[EC 1.14.14.43 created 2017]

EC 1.14.14.44

Accepted name: phenylacetaldehyde oxime monooxygenase

Reaction: (E)-phenylacetaldehyde oxime + [reduced NADPH—hemoprotein reductase] + O2 = (R)-mandelonitrile + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) (E)-phenylacetaldehyde oxime = (Z)-phenylacetaldehyde oxime
(1b) (Z)-phenylacetaldehyde oxime = phenylacetonitrile + H2O
(1c) phenylacetonitrile + [reduced NADPH—hemoprotein reductase] + O2 = (R)-mandelonitrile + [oxidized NADPH—hemoprotein reductase] + H2O

Glossary: (R)-mandelonitrile = (2R)-hydroxy(phenyl)acetonitrile

Other name(s): CYP71AN24 (gene name)

Systematic name: (E)-phenylacetaldehyde oxime,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase

Comments: This cytochrome P-450 (heme-thiolate) enzyme is involved in the biosynthesis of the cyanogenic glucosides (R)-prunasin and (R)-amygdalin. It catalyses three different activities - isomerization of the (E) isomer to the (Z) isomer, dehydration, and C-hydroxylation.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Yamaguchi, T., Yamamoto, K. and Asano, Y. Identification and characterization of CYP79D16 and CYP71AN24 catalyzing the first and second steps in L-phenylalanine-derived cyanogenic glycoside biosynthesis in the Japanese apricot, Prunus mume Sieb. et Zucc. Plant Mol. Biol. 86 (2014) 215-223. [PMID: 25015725]

[EC 1.14.14.44 created 2017]

EC 1.14.14.45

Accepted name: aromatic aldoxime N-monooxygenase

Reaction: (1) (E)-indol-3-ylacetaldehyde oxime + [reduced NADPH—hemoprotein reductase] + glutathione + O2 = S-[(E)-N-hydroxy(indol-3-yl)acetimidoyl]-L-glutathione + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) (E)-indol-3-ylacetaldehyde oxime + [reduced NADPH—hemoprotein reductase] + O2 = 1-(1H-indol-3-yl)-2-aci-nitroethane + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) 1-(1H-indol-3-yl)-2-aci-nitroethane + glutathione = S-[(E)-N-hydroxy(indol-3-yl)acetimidoyl]-L-glutathione + H2O (spontaneous)
(2) (E)-phenylacetaldehyde oxime + [reduced NADPH—hemoprotein reductase] + glutathione + O2 = S-[(Z)-N-hydroxy(phenyl)acetimidoyl]-L-glutathione + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(2a) (E)-phenylacetaldehyde oxime + [reduced NADPH—hemoprotein reductase] + O2 = 1-aci-nitro-2-phenylethane + [oxidized NADPH—hemoprotein reductase] + H2O
(2b) 1-aci-nitro-2-phenylethane + glutathione = S-[(Z)-N-hydroxy(phenyl)acetimidoyl]-L-glutathione + H2O (spontaneous)

Other name(s): CYP83B1 (gene name)

Systematic name: (E)-indol-3-ylacetaldoxime,[reduced NADPH—hemoprotein reductase],glutathione:oxygen oxidoreductase (oxime-hydroxylating)

Comments: This cytochrome P-450 (heme thiolate) enzyme is involved in the biosynthesis of glucosinolates in plants. The enzyme catalyses the N-hydroxylation of aromatic aldoximes derived from L-tryptophan, L-phenylalanine, and L-tyrosine, forming an aci-nitro intermediate that reacts non-enzymically with glutathione to produce an N-alkyl-thiohydroximate adduct, the committed precursor of glucosinolates. In the absence of glutathione, the enzyme is suicidal, probably due to interaction of the reactive aci-nitro compound with catalytic residues in the active site.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Bak, S., Tax, F.E., Feldmann, K.A., Galbraith, D.W. and Feyereisen, R. CYP83B1, a cytochrome P450 at the metabolic branch point in auxin and indole glucosinolate biosynthesis in Arabidopsis. Plant Cell 13 (2001) 101-111. [PMID: 11158532]

2. Naur, P., Petersen, B.L., Mikkelsen, M.D., Bak, S., Rasmussen, H., Olsen, C.E. and Halkier, B.A. CYP83A1 and CYP83B1, two nonredundant cytochrome P450 enzymes metabolizing oximes in the biosynthesis of glucosinolates in Arabidopsis. Plant Physiol. 133 (2003) 63-72. [PMID: 12970475]

3. Geu-Flores, F., Møldrup, M.E., Böttcher, C., Olsen, C.E., Scheel, D. and Halkier, B.A. Cytosolic γ-glutamyl peptidases process glutathione conjugates in the biosynthesis of glucosinolates and camalexin in Arabidopsis. Plant Cell 23 (2011) 2456-2469. [PMID: 21712415]

[EC 1.14.14.45 created 2017]

EC 1.14.14.46

Accepted name: pimeloyl-[acyl-carrier protein] synthase

Reaction: a long-chain acyl-[acyl-carrier protein] + 2 reduced flavodoxin + 3 O2 = pimeloyl-[acyl-carrier protein] + an n-alkanal + 2 oxidized flavodoxin + 3 H2O (overall reaction)
(1a) a long-chain acyl-[acyl-carrier protein] + reduced flavodoxin + O2 = a (7S)-7-hydroxy-long-chain-acyl-[acyl-carrier protein] + oxidized flavodoxin + H2O
(1b) a (7S)-7-hydroxy-long-chain-acyl-[acyl-carrier protein] + reduced flavodoxin + O2 = a (7R,8R)-7,8-dihydroxy-long-chain-acyl-[acyl-carrier protein] + oxidized flavodoxin + H2O
(1c) a (7R,8R)-7,8-dihydroxy-long-chain-acyl-[acyl-carrier protein] + reduced flavodoxin + O2 = a 7-oxoheptanoyl-[acyl-carrier protein] + an n-alkanal + oxidized flavodoxin + 2 H2O
(1d) a 7-oxoheptanoyl-[acyl-carrier protein] + oxidized flavodoxin + H2O = a pimeloyl-[acyl-carrier protein] + reduced flavodoxin + H+

Glossary: a long-chain acyl-[acyl-carrier protein] = an acyl-[acyl-carrier protein] thioester where the acyl chain contains 13 to 22 carbon atoms.
palmitoyl-[acyl-carrier protein] = hexadecanoyl-[acyl-carrier protein]
pimeloyl-[acyl-carrier protein] = 6-carboxyhexanoyl-[acyl-carrier protein]

Other name(s): bioI (gene name); P450BioI; CYP107H1

Systematic name: acyl-[acyl-carrier protein],reduced-flavodoxin:oxygen oxidoreductase (pimeloyl-[acyl-carrier protein] forming)

Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme catalyses an oxidative C-C bond cleavage of long-chain acyl-[acyl-carrier protein]s of various lengths to generate pimeloyl-[acyl-carrier protein], an intermediate in the biosynthesis of biotin. The preferred substrate of the enzyme from the bacterium Bacillus subtilis is palmitoyl-[acyl-carrier protein] which then gives heptanal as the alkanal. The mechanism is similar to EC 1.14.15.6, cholesterol monooxygenase (side-chain-cleaving), followed by a hydroxylation step, which may occur spontaneously [2].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Stok, J.E. and De Voss, J. Expression, purification, and characterization of BioI: a carbon-carbon bond cleaving cytochrome P450 involved in biotin biosynthesis in Bacillus subtilis. Arch. Biochem. Biophys. 384 (2000) 351-360. [PMID: 11368323]

2. Cryle, M.J. and De Voss, J.J. Carbon-carbon bond cleavage by cytochrome p450(BioI)(CYP107H1). Chem. Commun. (Camb.) (2004) 86-87. [PMID: 14737344]

3. Cryle, M.J. and Schlichting, I. Structural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450(BioI) ACP complex. Proc. Natl. Acad. Sci. USA 105 (2008) 15696-15701. [PMID: 18838690]

4. Cryle, M.J. Selectivity in a barren landscape: the P450(BioI)-ACP complex. Biochem. Soc. Trans. 38 (2010) 934-939. [PMID: 20658980]

[EC 1.14.14.46 created 2013 as EC 1.14.15.12, transferred 2017 to EC 1.14.14.46]

EC 1.14.14.47

Accepted name: nitric-oxide synthase (flavodoxin)

Reaction: 2 L-arginine + 3 reduced flavodoxin + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 oxidized flavodoxin + 4 H2O (overall reaction)
(1a) 2 L-arginine + 2 reduced flavodoxin + 2 O2 = 2 Nω-hydroxy-L-arginine + 2 oxidized flavodoxin + 2 H2O
(1b) 2 Nω-hydroxy-L-arginine + reduced flavodoxin + 2 O2 = 2 L-citrulline + 2 nitric oxide + oxidized flavodoxin + 2 H2O

Glossary: nitric oxide = NO = nitrogen(II) oxide

Other name(s): nitric oxide synthetase (ambiguous); NO synthase (ambiguous)

Systematic name: L-arginine,reduced-flavodoxin:oxygen oxidoreductase (nitric-oxide-forming)

Comments: Binds heme (iron protoporphyrin IX) and tetrahydrobiopterin. The enzyme, found in bacteria and archaea, consist of only an oxygenase domain and functions together with bacterial ferredoxins or flavodoxins. The orthologous enzymes from plants and animals also contain a reductase domain and use only NADPH as the electron donor (cf. EC 1.14.13.39).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Pant, K., Bilwes, A.M., Adak, S., Stuehr, D.J. and Crane, B.R. Structure of a nitric oxide synthase heme protein from Bacillus subtilis. Biochemistry 41 (2002) 11071-11079. [PMID: 12220171]

2. Adak, S., Aulak, K.S. and Stuehr, D.J. Direct evidence for nitric oxide production by a nitric-oxide synthase-like protein from Bacillus subtilis. J. Biol. Chem. 277 (2002) 16167-16171. [PMID: 11856757]

3. Wang, Z.Q., Lawson, R.J., Buddha, M.R., Wei, C.C., Crane, B.R., Munro, A.W. and Stuehr, D.J. Bacterial flavodoxins support nitric oxide production by Bacillus subtilis nitric-oxide synthase. J. Biol. Chem. 282 (2007) 2196-2202. [PMID: 17127770]

4. Agapie, T., Suseno, S., Woodward, J.J., Stoll, S., Britt, R.D. and Marletta, M.A. NO formation by a catalytically self-sufficient bacterial nitric oxide synthase from Sorangium cellulosum. Proc. Natl. Acad. Sci. USA 106 (2009) 16221-16226. [PMID: 19805284]

5. Holden, J.K., Lim, N. and Poulos, T.L. Identification of redox partners and development of a novel chimeric bacterial nitric oxide synthase for structure activity analyses. J. Biol. Chem. 289 (2014) 29437-29445. [PMID: 25194416]

[EC 1.14.14.47 created 2012 as EC 1.14.13.165, transferred 2017 to EC 1.14.14.47]

EC 1.14.14.48

Accepted name: jasmonoyl-L-amino acid 12-hydroxylase

Reaction: a jasmonoyl-L-amino acid + [reduced NADPH —hemoprotein reductase] + O2 = a 12-hydroxyjasmonoyl-L-amino acid + [oxidized NADPH —hemoprotein reductase] + H2O

Glossary: jasmonic acid = {(1R,2R)-3-oxo-2-[(2Z)pent-2-en-1-yl]cyclopentyl}acetic acid
(+)-7-epi-jasmonic acid = {(1R,2S)-3-oxo-2-[(2Z)pent-2-en-1-yl]cyclopentyl}acetic acid

Other name(s): CYP94B1 (gene name); CYP94B3 (gene name)

Systematic name: jasmonoyl-L-amino acid,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (12-hydroxylating)

Comments: A cytochrome P450 (heme thiolate) enzyme found in plants. The enzyme acts on jasmonoyl-L-amino acid conjugates, catalysing the hydroxylation of the C-12 position of jasmonic acid. While the best studied substrate is (+)-7-epi-jasmonoyl-L-isoleucine, the enzyme was shown to be active with jasmonoyl-L-valine and jasmonoyl-L-phenylalanine, and is likely to be active with other jasmonoyl-amino acid conjugates.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Koo, A.J., Cooke, T.F. and Howe, G.A. Cytochrome P450 CYP94B3 mediates catabolism and inactivation of the plant hormone jasmonoyl-L-isoleucine. Proc. Natl. Acad. Sci. USA 108 (2011) 9298-9303. [PMID: 21576464]

2. Kitaoka, N., Matsubara, T., Sato, M., Takahashi, K., Wakuta, S., Kawaide, H., Matsui, H., Nabeta, K. and Matsuura, H. Arabidopsis CYP94B3 encodes jasmonyl-L-isoleucine 12-hydroxylase, a key enzyme in the oxidative catabolism of jasmonate. Plant Cell Physiol 52 (2011) 1757-1765. [PMID: 21849397]

3. Heitz, T., Widemann, E., Lugan, R., Miesch, L., Ullmann, P., Desaubry, L., Holder, E., Grausem, B., Kandel, S., Miesch, M., Werck-Reichhart, D. and Pinot, F. Cytochromes P450 CYP94C1 and CYP94B3 catalyze two successive oxidation steps of plant hormone jasmonoyl-isoleucine for catabolic turnover. J. Biol. Chem. 287 (2012) 6296-6306. [PMID: 22215670]

4. Kitaoka, N., Kawaide, H., Amano, N., Matsubara, T., Nabeta, K., Takahashi, K. and Matsuura, H. CYP94B3 activity against jasmonic acid amino acid conjugates and the elucidation of 12-O-β-glucopyranosyl-jasmonoyl-L-isoleucine as an additional metabolite. Phytochemistry 99 (2014) 6-13. [PMID: 24467969]

5. Koo, A.J., Thireault, C., Zemelis, S., Poudel, A.N., Zhang, T., Kitaoka, N., Brandizzi, F., Matsuura, H. and Howe, G.A. Endoplasmic reticulum-associated inactivation of the hormone jasmonoyl-L-isoleucine by multiple members of the cytochrome P450 94 family in Arabidopsis. J. Biol. Chem. 289 (2014) 29728-29738. [PMID: 25210037]

6. Widemann, E., Grausem, B., Renault, H., Pineau, E., Heinrich, C., Lugan, R., Ullmann, P., Miesch, L., Aubert, Y., Miesch, M., Heitz, T. and Pinot, F. Sequential oxidation of jasmonoyl-phenylalanine and jasmonoyl-isoleucine by multiple cytochrome P450 of the CYP94 family through newly identified aldehyde intermediates. Phytochemistry 117 (2015) 388-399. [PMID: 26164240]

[EC 1.14.14.48 created 2017]

EC 1.14.14.49

Accepted name: 12-hydroxyjasmonoyl-L-amino acid 12-hydroxylase

Reaction: a 12-hydroxyjasmonoyl-L-amino acid + 2 [reduced NADPH —hemoprotein reductase] + 2 O2 = a 12-hydroxy-12-oxojasmonoyl-L-amino acid + 2 [oxidized NADPH —hemoprotein reductase] + 3 H2O (overall reaction)
(1a) a 12-hydroxyjasmonoyl-L-amino acid + [reduced NADPH —hemoprotein reductase] + O2 = a 12-oxojasmonoyl-L-amino acid + [oxidized NADPH —hemoprotein reductase] + 2 H2O
(1b) a 12-oxojasmonoyl-L-amino acid + [reduced NADPH —hemoprotein reductase] + O2 = a 12-hydroxy-12-oxojasmonoyl-L-amino acid + [oxidized NADPH —hemoprotein reductase] + H2O

Glossary: (3Z)-5-[(1R,2R)-2-(carboxymethyl)-5-oxocyclopentyl]pent-3-enoate = 12-hydroxy-12-oxojasmonate

Other name(s): CYP94C1 (gene name)

Systematic name: 12-hydroxyjasmonoyl-L-amino acid,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (12-hydroxylating)

Comments: A cytochrome P450 (heme thiolate) enzyme found in plants. The enzyme acts on jasmonoyl-L-amino acid conjugates that have been hydroxylated at the C-12 position of jasmonic acid by EC 1.14.14.48, jasmonoyl-L-amino acid 12-hydroxylase, further oxidizing that position to a carboxylate via an aldehyde intermediate. While the best studied substrate is (+)-7-epi-jasmonoyl-L-isoleucine, the enzyme was shown to be active with jasmonoyl-L-phenylalanine, and is likely to be active with other jasmonoyl-amino acid conjugates.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Heitz, T., Widemann, E., Lugan, R., Miesch, L., Ullmann, P., Desaubry, L., Holder, E., Grausem, B., Kandel, S., Miesch, M., Werck-Reichhart, D. and Pinot, F. Cytochromes P450 CYP94C1 and CYP94B3 catalyze two successive oxidation steps of plant hormone jasmonoyl-isoleucine for catabolic turnover. J. Biol. Chem. 287 (2012) 6296-6306. [PMID: 22215670]

2. Widemann, E., Grausem, B., Renault, H., Pineau, E., Heinrich, C., Lugan, R., Ullmann, P., Miesch, L., Aubert, Y., Miesch, M., Heitz, T. and Pinot, F. Sequential oxidation of jasmonoyl-phenylalanine and jasmonoyl-isoleucine by multiple cytochrome P450 of the CYP94 family through newly identified aldehyde intermediates. Phytochemistry 117 (2015) 388-399. [PMID: 26164240]

3. Bruckhoff, V., Haroth, S., Feussner, K., Konig, S., Brodhun, F. and Feussner, I. Functional characterization of CYP94-genes and identification of a novel jasmonate catabolite in flowers. PLoS One 11 (2016) e0159875. [PMID: 27459369]

[EC 1.14.14.49 created 2017]

EC 1.14.14.50

Accepted name: tabersonine 3-oxygenase

Reaction: (1) 16-methoxytabersonine + [reduced NADPH —hemoprotein reductase] + O2 = (3R)-3-hydroxy-16-methoxy-1,2-didehydro-2,3-dihydrotabersonine + [oxidized NADPH —hemoprotein reductase] + H2O
(2) tabersonine + [reduced NADPH —hemoprotein reductase] + O2 = (3R)-3-hydroxy-1,2-didehydro-2,3-dihydrotabersonine + [oxidized NADPH —hemoprotein reductase] + H2O

For diagram of reaction, click here

Other name(s): T3O; CYP71D1V2

Systematic name: 16-methoxytabersonine,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (3-hydroxylating)

Comments: This cytochrome P-450 (heme thiolate) enzyme acts on 16-methoxytabersonine, leading to biosynthesis of vindoline in the plant Catharanthus roseus (Madagascar periwinkle). It can also act on tabersonine, resulting in the production of small amounts of vindorosine. The products are unstable and, in the absence of EC 1.1.99.41, 3-hydroxy-1,2-didehydro-2,3-dihydrotabersonine reductase, will convert into 3-epoxylated compounds.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Qu, Y., Easson, M.L., Froese, J., Simionescu, R., Hudlicky, T. and De Luca, V. Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast. Proc. Natl Acad. Sci. USA 112 (2015) 6224-6229. [PMID: 25918424]

[EC 1.14.14.50 created 2017]

EC 1.14.14.51

Accepted name: (S)-limonene 6-monooxygenase

Reaction: (S)-limonene + [reduced NADPH —hemoprotein reductase] + O2 = (–)-trans-carveol + [oxidized NADPH —hemoprotein reductase] + H2O

For diagram of reaction click here

Glossary: limonene = a monoterpenoid
(S)-limonene = (–)-limonene

Other name(s): (–)-limonene 6-hydroxylase; (–)-limonene 6-monooxygenase; (–)-limonene,NADPH:oxygen oxidoreductase (6-hydroxylating)

Systematic name: (S)-limonene,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (6-hydroxylating)

Comments: A cytochrome P-450 (heme thiolate) enzyme. The enzyme participates in the biosynthesis of (–)-carvone, which is responsible for the aroma of spearmint.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Karp, F., Mihaliak, C.A., Harris, J.L. and Croteau, R. Monoterpene biosynthesis: specificity of the hydroxylations of (–)-limonene by enzyme preparations from peppermint (Mentha piperita), spearmint (Mentha spicata), and perilla (Perilla frutescens) leaves. Arch. Biochem. Biophys. 276 (1990) 219-226. [PMID: 2297225]

[EC 1.14.14.51 created 1992 as 1.14.13.48, modified 2003, transferred 2017 to EC 1.14.14.51]

EC 1.14.14.52

Accepted name: (S)-limonene 7-monooxygenase

Reaction: (S)-limonene + [reduced NADPH —hemoprotein reductase] + O2 = (–)-perillyl alcohol + [oxidized NADPH —hemoprotein reductase] + H2O

For diagram of reaction click here

Glossary: limonene = a monoterpenoid
(S)-limonene = (–)-limonene

Other name(s): (–)-limonene 7-monooxygenase; (–)-limonene hydroxylase; (–)-limonene monooxygenase; (–)-limonene,NADPH:oxygen oxidoreductase (7-hydroxylating)

Systematic name: (S)-limonene,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (7-hydroxylating)

Comments: A cytochrome P-450 (heme thiolate) enzyme. The enzyme, characterized from the plant Perilla frutescens, participates in the biosynthesis of perillyl aldehyde, the major constituent of the essential oil that accumulates in the glandular trichomes of this plant. Some forms of the enzyme also catalyse the oxidation of (–)-perillyl alcohol to (–)-perillyl aldehyde.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Karp, F., Mihaliak, C.A., Harris, J.L. and Croteau, R. Monoterpene biosynthesis: specificity of the hydroxylations of (–)-limonene by enzyme preparations from peppermint (Mentha piperita), spearmint (Mentha spicata), and perilla (Perilla frutescens) leaves. Arch. Biochem. Biophys. 276 (1990) 219-226. [PMID: 2297225]

2. Mau, C.J., Karp, F., Ito, M., Honda, G. and Croteau, R.B. A candidate cDNA clone for (–)-limonene-7-hydroxylase from Perilla frutescens. Phytochemistry 71 (2010) 373-379. [PMID: 20079506]

3. Fujiwara, Y. and Ito, M. Molecular cloning and characterization of a Perilla frutescens cytochrome P450 enzyme that catalyzes the later steps of perillaldehyde biosynthesis. Phytochemistry 134 (2017) 26-37. [PMID: 27890582]

[EC 1.14.14.52 created 1992 as 1.14.13.49, modified 2003, transferred 2017 to EC 1.14.14.52]

EC 1.14.14.53

Accepted name: (R)-limonene 6-monooxygenase

Reaction: (R)-limonene + [reduced NADPH —hemoprotein reductase] + O2 = (+)-trans-carveol + [oxidized NADPH —hemoprotein reductase] + H2O

For diagram of reaction click here

Glossary: limonene = a monoterpenoid
(R)-limonene = (+)-limonene

Other name(s): (+)-limonene-6-hydroxylase; (+)-limonene 6-monooxygenase

Systematic name: (R)-limonene,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (6-hydroxylating)

Comments: The reaction is stereospecific with over 95% yield of (+)-trans-carveol from (R)-limonene. (S)-Limonene, the substrate for EC 1.14.14.51, (S)-limonene 6-monooxygenase, is not a substrate. Forms part of the carvone biosynthesis pathway in Carum carvi (caraway) seeds.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Bouwmeester, H.J., Gershenzon, J., Konings, M.C.J.M. and Croteau, R. Biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway. I. Demonstration of enzyme activities and their changes with development. Plant Physiol. 117 (1998) 901-912. [PMID: 9662532]

2. Bouwmeester, H.J., Konings, M.C.J.M., Gershenzon, J., Karp, F. and Croteau, R. Cytochrome P-450 dependent (+)-limonene-6-hydroxylation in fruits of caraway (Carum carvi). Phytochemistry 50 (1999) 243-248.

[EC 1.14.14.53 created 2003 as EC 1.14.13.80, transferred 2017 to EC 1.14.14.53]

EC 1.14.14.54

Accepted name: phenylacetate 2-hydroxylase

Reaction: phenylacetate + [reduced NADPH —hemoprotein reductase] + O2 = (2-hydroxyphenyl)acetate + [oxidized NADPH —hemoprotein reductase] + H2O

Other name(s): CYP504; phaA (gene name)

Systematic name: phenylacetate,[reduced NADPH —hemoprotein reductase]:oxygen oxidoreductase (2-hydroxylating)

Comments: This cytochrome P-450 (heme-thiolate) enzyme, found in Aspergillus nidulans, is involved in the degradation of phenylacetate.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mingot, J.M., Penalva, M.A. and Fernandez-Canon, J.M. Disruption of phacA, an Aspergillus nidulans gene encoding a novel cytochrome P450 monooxygenase catalyzing phenylacetate 2-hydroxylation, results in penicillin overproduction. J. Biol. Chem. 274 (1999) 14545-14550. [PMID: 10329644]

2. Rodriguez-Saiz, M., Barredo, J.L., Moreno, M.A., Fernandez-Canon, J.M., Penalva, M.A. and Diez, B. Reduced function of a phenylacetate-oxidizing cytochrome P450 caused strong genetic improvement in early phylogeny of penicillin-producing strains. J. Bacteriol. 183 (2001) 5465-5471. [PMID: 11544206]

[EC 1.14.14.54 created 2017]


EC 1.14.15 With a reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.15.1 camphor 5-monooxygenase
EC 1.14.15.2 now EC 1.14.13.162
EC 1.14.15.3 alkane 1-monooxygenase
EC 1.14.15.4 steroid 11β-monooxygenase
EC 1.14.15.5 corticosterone 18-monooxygenase
EC 1.14.15.6 cholesterol monooxygenase (side-chain-cleaving)
EC 1.14.15.7 choline monooxygenase
EC 1.14.15.8 steroid 15β-monooxygenase
EC 1.14.15.9 spheroidene monooxygenase
EC 1.14.15.10 (+)-camphor 6-endo-hydroxylase
EC 1.14.15.11 pentalenic acid synthase
EC 1.14.15.12 transferred, now EC 1.14.14.46
EC 1.14.15.13 pulcherriminic acid synthase
EC 1.14.15.14 methyl-branched lipid ω-hydroxylase
EC 1.14.15.15 cholestanetriol 26-monooxygenase
EC 1.14.15.16 vitamin D3 24-hydroxylase
EC 1.14.15.17 pheophorbide-a oxygenase
EC 1.14.15.18 calcidiol 1-monooxygenase
EC 1.14.15.19 C-19 steroid 1α-hydroxylase
EC 1.14.15.20 heme oxygenase (biliverdin-producing, ferredoxin)
EC 1.14.15.21 zeaxanthin epoxidase
EC 1.14.15.22 vitamin D 1,25-hydroxylase
EC 1.14.15.23 chloroacetanilide N-alkylformylase

EC 1.14.15.1

Accepted name: camphor 5-monooxygenase

Reaction: (+)-camphor + reduced putidaredoxin + O2 = (+)-exo-5-hydroxycamphor + oxidized putidaredoxin + H2O

For diagram of reaction click here.

Other name(s): camphor 5-exo-methylene hydroxylase; 2-bornanone 5-exo-hydroxylase; bornanone 5-exo-hydroxylase; camphor 5-exo-hydroxylase; camphor 5-exohydroxylase; camphor hydroxylase; d-camphor monooxygenase; methylene hydroxylase; methylene monooxygenase; D-camphor-exo-hydroxylase; camphor methylene hydroxylase

Systematic name: (+)-camphor,reduced putidaredoxin:oxygen oxidoreductase (5-hydroxylating)

Comments: A heme-thiolate protein (P-450). Also acts on (–)-camphor and 1,2-campholide, forming 5-exo-hydroxy-1,2-campholide.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 9030-82-4

References:

1. Hedegaard, J. and Gunsalus, I.C. Mixed function oxidation. IV. An induced methylene hydroxylase in camphor oxidation. J. Biol. Chem. 240 (1965) 4038-4043. [PMID: 4378858]

2. Tyson, C.A., Lipscomb, J.D. and Gunsalus, I.C. The role of putidaredoxin and P450cam in methylene hydroxylation. J. Biol. Chem. 247 (1972) 5777-5784. [PMID: 4341491]

[EC 1.14.15.1 created 1972, modified 1986]

[EC 1.14.15.2 Transferred entry: camphor 1,2-monooxygenase. Now EC 1.14.13.162, 2,5-diketocamphane 1,2-monooxygenase. (EC 1.14.15.2 created 1972, deleted 2012)]

EC 1.14.15.3

Accepted name: alkane 1-monooxygenase

Reaction: octane + 2 reduced rubredoxin + O2 + 2 H+ = 1-octanol + 2 oxidized rubredoxin + H2O

Other name(s): alkane 1-hydroxylase; ω-hydroxylase; fatty acid ω-hydroxylase; alkane monooxygenase; 1-hydroxylase; alkane hydroxylase

Systematic name: alkane,reduced-rubredoxin:oxygen 1-oxidoreductase

Comments: Some enzymes in this group are heme-thiolate proteins (P-450). Also hydroxylates fatty acids in the ω-position.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, UM-BBD, CAS registry number: 9059-16-9

References:

1. Cardini, G. and Jurtshuk, P. The enzymatic hydroxylation of n-octane by Corynebacterium sp. strain 7E1C. J. Biol. Chem. 245 (1970) 2789-2796. [PMID: 4317878]

2. McKenna, E.J. and Coon, M.J. Enzymatic ω-oxidation. IV. Purification and properties of the ω-hydroxylase of Pseudomonas oleovorans. J. Biol. Chem. 245 (1970) 3882-3889. [PMID: 4395379]

3. Peterson, J.A., Kusunose, M., Kusunose, E. and Coon, M.J. Enzymatic ω-oxidation. II. Function of rubredoxin as the electron carrier in ω-hydroxylation. J. Biol. Chem. 242 (1967) 4334-4340. [PMID: 4294330]

[EC 1.14.15.3 created 1972]

EC 1.14.15.4

Accepted name: steroid 11β-monooxygenase

Reaction: a steroid + 2 reduced adrenodoxin + O2 + 2 H+ = an 11β-hydroxysteroid + 2 oxidized adrenodoxin + H2O

Other name(s): steroid 11β-hydroxylase; steroid 11β/18-hydroxylase

Systematic name: steroid,reduced-adrenodoxin:oxygen oxidoreductase (11β-hydroxylating)

Comments: A heme-thiolate protein (P-450). Also hydroxylates steroids at the 18-position, and converts 18-hydroxycorticosterone into aldosterone.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9029-66-7

References:

1. Grant, J.K. and Brownie, A.C. The role of fumarate and TPN in steroid enzymic 11β-hydroxylation. Biochim. Biophys. Acta 18 (1955) 433-434. [PMID: 13276417]

2. Hayano, M. and Dorfman, R.I. On the mechanism of the C-11β-hydroxylation of steroids. J. Biol. Chem. 211 (1954) 227-235. [PMID: 13211659]

3. Tomkins, G.M., Michael, P.J. and Curran, J.F. Studies on the nature of steroid 11β-hydroxylation. Biochim. Biophys. Acta 23 (1957) 655-656. [PMID: 13426185]

4. Yanagibashi, K., Haniu, M., Shively, J.E., Shen, W.H. and Hall, P. The synthesis of aldosterone by the adrenal cortex. Two zones (fasciculata and glomerulosa) possess one enzyme for 11β-, 18-hydroxylation, and aldehyde synthesis. J. Biol. Chem. 261 (1986) 3556-3562. [PMID: 3485096]

5. Zuidweg, M.H.J. Hydroxylation of Reichstein's compound S with cell-free preparations from Curvularia lunata. Biochim. Biophys. Acta 152 (1968) 144-158. [PMID: 4967077]

[EC 1.14.15.4 created 1961 as EC 1.99.1.7, transferred 1965 to EC 1.14.1.6, transferred 1972 to EC 1.14.15.4, modified 1989, modified 2014]

EC 1.14.15.5

Accepted name: corticosterone 18-monooxygenase

Reaction: corticosterone + 2 reduced adrenodoxin + O2 + 2 H+ = 18-hydroxycorticosterone + 2 oxidized adrenodoxin + H2O

Other name(s): corticosterone 18-hydroxylase; corticosterone methyl oxidase; corticosterone,reduced-adrenal-ferredoxin:oxygen oxidoreductase (18-hydroxylating

Systematic name: corticosterone,reduced-adrenodoxin:oxygen oxidoreductase (18-hydroxylating)

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-75-0

References:

1. Raman, P.B., Sharma, D.C. and Dorfman, R.I. Studies on aldosterone biosynthesis in vitro. Biochemistry 5 (1966) 1795.

[EC 1.14.15.5 created 1972]

EC 1.14.15.6

Accepted name: cholesterol monooxygenase (side-chain-cleaving)

Reaction: cholesterol + 6 reduced adrenodoxin + 3 O2 + 6 H+ = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O (overall reaction)
(1a) cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O
(1b) (22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O
(1c) (20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O

Other name(s): cholesterol desmolase; cytochrome P-450scc; C27-side chain cleavage enzyme; cholesterol 20-22-desmolase; cholesterol C20-22 desmolase; cholesterol side-chain cleavage enzyme; cholesterol side-chain-cleaving enzyme; steroid 20-22 desmolase; steroid 20-22-lyase; CYP11A1 (gene name)

Systematic name: cholesterol,reduced-adrenodoxin:oxygen oxidoreductase (side-chain-cleaving)

Comments: A heme-thiolate protein (cytochrome P-450). The reaction proceeds in three stages, with two hydroxylations at C-22 and C-20 preceding scission of the side-chain between carbons 20 and 22. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 37292-81-2, 440354-98-3

References:

1. Burstein, S., Middleditch, B.S. and Gut, M. Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation. J. Biol. Chem. 250 (1975) 9028-9037. [PMID: 1238395]

2. Hanukoglu, I., Spitsberg, V., Bumpus, J.A., Dus, K.M. and Jefcoate, C.R. Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover. J. Biol. Chem. 256 (1981) 4321-4328. [PMID: 7217084]

3. Hanukoglu, I. and Hanukoglu, Z. Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation. Eur. J. Biochem. 157 (1986) 27-31. [PMID: 3011431]

4. Strushkevich, N., MacKenzie, F., Cherkesova, T., Grabovec, I., Usanov, S. and Park, H.W. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc. Natl. Acad. Sci. USA 108 (2011) 10139-10143. [PMID: 21636783]

5. Mast, N., Annalora, A.J., Lodowski, D.T., Palczewski, K., Stout, C.D. and Pikuleva, I.A. Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J. Biol. Chem. 286 (2011) 5607-5613. [PMID: 21159775]

[EC 1.14.15.6 created 1983, modified 2013, modified 2014]

EC 1.14.15.7

Accepted name: choline monooxygenase

Reaction: choline + O2 + 2 reduced ferredoxin + 2 H+ = betaine aldehyde hydrate + H2O + 2 oxidized ferredoxin

Glossary: betaine = glycine betaine = N,N,N-trimethylammonioacetate
betaine aldehyde = N,N,N-trimethyl-2-oxoethylammonium
choline = (2-hydroxyethyl)trimethylammonium

Systematic name: choline,reduced-ferredoxin:oxygen oxidoreductase

Comments: The spinach enzyme, which is located in the chloroplast, contains a Rieske-type [2Fe-2S] cluster, and probably also a mononuclear Fe centre. Requires Mg2+. Catalyses the first step of glycine betaine synthesis. In many bacteria, plants and animals, betaine is synthesized in two steps: (1) choline to betaine aldehyde and (2) betaine aldehyde to betaine. Different enzymes are involved in the first reaction. In plants, the reaction is catalysed by this enzyme whereas in animals and many bacteria it is catalysed by either membrane-bound EC 1.1.99.1 (choline dehydrogenase) or soluble EC 1.1.3.17 (choline oxidase) [7]. The enzyme involved in the second step, EC 1.2.1.8 (betaine-aldehyde dehydrogenase), appears to be the same in plants, animals and bacteria. In some bacteria, betaine is synthesized from glycine through the actions of EC 2.1.1.156 (glycine/sarcosine N-methyltransferase) and EC 2.1.1.157 (sarcosine/dimethylglycine N-methyltransferase).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 118390-76-4

References:

1. Brouquisse, R., Weigel, P., Rhodes, D., Yocum, C.F. and Hanson, A.D. Evidence for a ferredoxin-dependent choline monooxygenase from spinach chloroplast stroma. Plant Physiol. 90 (1989) 322-329. [PMID: 16666757]

2. Burnet, M., Lafontaine, P.J. and Hanson, A.D. Assay, purification, and partial characterization of choline monooxygenase from spinach. Plant Physiol. 108 (1995) 581-588. [PMID: 12228495]

3. Rathinasabapathi, B., Burnet, M., Russell, B.L., Gage, D.A., Liao, P., Nye, G.J., Scott, P., Golbeck, J.H. and Hanson, A.D. Choline monooxygenase, an unusual iron-sulfur enzyme catalyzing the first step of glycine betaine synthesis in plants: Prosthetic group characterization and cDNA cloning. Proc. Natl. Acad. Sci. USA 94 (1997) 3454-3458. [PMID: 9096415]

4. Russell, B.L., Rathinasabapathi, B. and Hanson, A.D. Osmotic stress induces expression of choline monooxygenase in sugar beet and amaranth. Plant Physiol. 116 (1998) 859-865. [PMID: 9489025]

5. Nuccio, M.L., Russell, B.L., Nolte, K.D., Rathinasabapathi, B., Gage, D.A. and Hanson, A.D. Glycine betaine synthesis in transgenic tobacco expressing choline monooxygenase is limited by the endogenous choline supply. Plant J. 16 (1998) 101-110.

6. Nuccio, M.L., Russell, B.L., Nolte, K.D., Rathinasabapathi, B., Gage, D.A. and Hanson, A.D. The endogenous choline supply limits glycine betaine synthesis in transgenic tobacco expressing choline. Plant J. 16 (1998) 487-496. [PMID: 9881168]

7. Waditee, R., Tanaka, Y., Aoki, K., Hibino, T., Jikuya, H., Takano, J., Takabe, T. and Takabe, T. Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J. Biol. Chem. 278 (2003) 4932-4942. [PMID: 12466265]

[EC 1.14.15.7 created 2001, modified 2002 (EC 1.14.14.4 created 2000, incorporated 2002), modified 2005, modified 2011]

EC 1.14.15.8

Accepted name: steroid 15β-monooxygenase

Reaction: progesterone + 2 reduced [2Fe-2S] ferredoxin + O2 = 15β-hydroxyprogesterone + 2 oxidized [2Fe-2S] ferredoxin + H2O

Other name(s): cytochrome P-450meg; cytochrome P450meg; steroid 15β-hydroxylase; CYP106A2; BmCYP106A2

Systematic name: progesterone,reduced-ferredoxin:oxygen oxidoreductase (15β-hydroxylating)

Comments: The enzyme from Bacillus megaterium hydroxylates a variety of 3-oxo-Δ4-steroids in position 15β. Ring A-reduced, aromatic, and 3β-hydroxy-Δ4-steroids do not serve as substrates [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Berg, A., Ingelman-Sundberg, M. and Gustafsson, J.A. Purification and characterization of cytochrome P-450meg. J. Biol. Chem. 254 (1979) 5264-5271. [PMID: 109432]

2. Berg, A., Gustafsson, J.A. and Ingelman-Sundberg, M. Characterization of a cytochrome P-450-dependent steroid hydroxylase system present in Bacillus megaterium. J. Biol. Chem. 251 (1976) 2831-2838. [PMID: 177422]

3. Lisurek, M., Kang, M.J., Hartmann, R.W. and Bernhardt, R. Identification of monohydroxy progesterones produced by CYP106A2 using comparative HPLC and electrospray ionisation collision-induced dissociation mass spectrometry. Biochem. Biophys. Res. Commun. 319 (2004) 677-682. [PMID: 15178459]

4. Goni, G., Zollner, A., Lisurek, M., Velazquez-Campoy, A., Pinto, S., Gomez-Moreno, C., Hannemann, F., Bernhardt, R. and Medina, M. Cyanobacterial electron carrier proteins as electron donors to CYP106A2 from Bacillus megaterium ATCC 13368. Biochim. Biophys. Acta 1794 (2009) 1635-1642. [PMID: 19635596]

5. Lisurek, M., Simgen, B., Antes, I. and Bernhardt, R. Theoretical and experimental evaluation of a CYP106A2 low homology model and production of mutants with changed activity and selectivity of hydroxylation. Chembiochem 9 (2008) 1439-1449. [PMID: 18481342]

[EC 1.14.15.8 created 2010]

EC 1.14.15.9

Accepted name: spheroidene monooxygenase

Reaction: (1) spheroidene + 2 reduced ferredoxin [iron-sulfur] cluster + 2 O2 = spheroiden-2-one + 2 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(1a) spheroidene + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2-hydroxyspheroidene + oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) 2-hydroxyspheroidene + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2,2-dihydroxyspheroidene + oxidized ferredoxin [iron-sulfur] cluster + H2O
(1c) 2,2-dihydroxyspheroidene = spheroiden-2-one + H2O (spontaneous)
(2) spirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 O2 = 2-oxospirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(2a) spirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2-hydroxyspirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(2b) 2-hydroxyspirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2,2-dihydroxyspirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(2c) 2,2-dihydroxyspirilloxanthin = 2-oxospirilloxanthin + H2O (spontaneous)
(3) 2-oxospirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 O2 = 2,2'-dioxospirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O (overall reaction)
(3a) 2-oxospirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2'-hydroxy-2-oxospirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(3b) 2'-hydroxy-2-oxospirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O2 + 2H+ = 2',2'-dihydroxy-2-oxospirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H2O
(3c) 2',2'-dihydroxy-2-oxospirilloxanthin = 2,2'-dioxospirilloxanthin + H2O (spontaneous)

For diagram of reaction click here or click here.

Glossary: spheroidene = 3,4-didehydro-1-methoxy-1,2,7',8'-tetrahydro-ψ,ψ-carotene

Other name(s): CrtA; acyclic carotenoid 2-ketolase; spirilloxanthin monooxygenase; 2-oxo-spirilloxanthin monooxygenase

Systematic name: spheroidene,reduced-ferredoxin:oxygen oxidoreductase (spheroiden-2-one-forming)

Comments: The enzyme is involved in spheroidenone biosynthesis and in 2,2'-dioxospirilloxanthin biosynthesis. The enzyme from Rhodobacter sphaeroides contains heme at its active site [1].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Lee, P.C., Holtzapple, E. and Schmidt-Dannert, C. Novel activity of Rhodobacter sphaeroides spheroidene monooxygenase CrtA expressed in Escherichia coli, Appl. Environ. Microbiol. 76 (2010) 7328-7331. [PMID: 20851979]

2. Gerjets, T., Steiger, S. and Sandmann, G. Catalytic properties of the expressed acyclic carotenoid 2-ketolases from Rhodobacter capsulatus and Rubrivivax gelatinosus, Biochim. Biophys. Acta 1791 (2009) 125-131. [PMID: 19136077]

[EC 1.14.15.9 created 2012, modified 2016]

EC 1.14.15.10

Accepted name: (+)-camphor 6-endo-hydroxylase

Reaction: (+)-camphor + reduced putidaredoxin + O2 = (+)-6-endo-hydroxycamphor + oxidized putidaredoxin + H2O

For diagram of reaction click here.

Other name(s): P450camr

Systematic name: (+)-camphor,reduced putidaredoxin:oxygen oxidoreductase (6-endo-hydroxylating)

Comments: A cytochrome P-450 monooxygenase from the bacterium Rhodococcus sp. NCIMB 9784.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Grogan, G., Roberts, G.A., Parsons, S., Turner, N.J. and Flitsch, S.L. P450camr, a cytochrome P450 catalysing the stereospecific 6-endo-hydroxylation of (1R)-(+)-camphor. Appl. Microbiol. Biotechnol. 59 (2002) 449-454. [PMID: 12172608]

[EC 1.14.15.10 created 2012]

EC 1.14.15.11

Accepted name: pentalenic acid synthase

Reaction: 1-deoxypentalenate + reduced ferredoxin + O2 = pentalenate + oxidized ferredoxin + H2O

For diagram of reaction click here.

Glossary: 1-deoxypentalenate = (1R,3aR,5aS,8aR)-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate
pentalenate = (1R,3aR,5aS,6R,8aS)-6-hydroxy-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate

Other name(s): CYP105D7; sav7469 (gene name); 1-deoxypentalenate,reduced ferredoxin:O2 oxidoreductase

Systematic name: 1-deoxypentalenate,reduced ferredoxin:oxygen oxidoreductase

Comments: A heme-thiolate enzyme (P-450). Isolated from the bacterium Streptomyces avermitilis. The product, pentalenate, is a co-metabolite from pentalenolactone biosynthesis.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Takamatsu, S., Xu, L.H., Fushinobu, S., Shoun, H., Komatsu, M., Cane, D.E. and Ikeda, H. Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone family of metabolites: hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis. J. Antibiot. (Tokyo) 64 (2011) 65-71. [PMID: 21081950]

[EC 1.14.15.11 created 2012]

[EC 1.14.15.12 Transferred entry: pimeloyl-[acyl-carrier protein] synthase, now EC 1.14.14.46, pimeloyl-[acyl-carrier protein] synthase (EC 1.14.15.12 created 2013, deleted 2017)]

EC 1.14.15.13

Accepted name: pulcherriminic acid synthase

Reaction: cyclo(L-leucyl-L-leucyl) + 6 reduced ferredoxin + 3 O2 = pulcherriminic acid + 6 oxidized ferredoxin + 4 H2O

For diagram of reaction click here.

Glossary: cyclo(L-leucyl-L-leucyl) = (3S,6S)-3,6-bis(2-methylpropyl)piperazine-2,5-dione
pulcherriminic acid = 2,5-dihydroxy-3,6-bis(2-methylpropyl)pyrazine bis-N-oxide

Other name(s): cyclo-L-leucyl-L-leucyl dipeptide oxidase; CYP134A1; CypX (ambiguous)

Systematic name: cyclo(L-leucyl-L-leucyl),reduced-ferredoxin:oxygen oxidoreductase (N-hydroxylating,aromatizing)

Comments: A heme-thiolate (P-450) enzyme from the bacterium Bacillus subtilis. The order of events during the overall reaction is unknown. Pulcherrimic acid spontaneously forms an iron chelate with Fe(3+) to form the red pigment pulcherrimin [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. MacDonald, J.C. Biosynthesis of pulcherriminic acid. Biochem. J. 96 (1965) 533-538. [PMID: 5837792]

2. Cryle, M.J., Bell, S.G. and Schlichting, I. Structural and biochemical characterization of the cytochrome P450 CypX (CYP134A1) from Bacillus subtilis: a cyclo-L-leucyl-L-leucyl dipeptide oxidase. Biochemistry 49 (2010) 7282-7296. [PMID: 20690619]

[EC 1.14.15.13 created 2013]

EC 1.14.15.14

Accepted name: methyl-branched lipid ω-hydroxylase

Reaction: a methyl-branched lipid + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = an ω-hydroxy-methyl-branched lipid + H2O + 2 oxidized ferredoxin [iron-sulfur] cluster

Other name(s): CYP124

Systematic name: methyl-branched lipid,reduced-ferredoxin:oxygen oxidoreductase (ω-hydroxylating)

Comments: The enzyme, found in pathogenic and nonpathogenic mycobacteria species, actinomycetes, and some proteobacteria, hydroxylates the ω-carbon of a number of methyl-branched lipids, including (2E,6E)-farnesol, phytanate, geranylgeraniol, 15-methylpalmitate and (2E,6E)-farnesyl diphosphate. It is a P-450 heme-thiolate enzyme.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Johnston, J.B., Kells, P.M., Podust, L.M. and Ortiz de Montellano, P.R. Biochemical and structural characterization of CYP124: a methyl-branched lipid ω-hydroxylase from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 106 (2009) 20687-20692. [PMID: 19933331]

[EC 1.14.15.14 created 2015]

EC 1.14.15.15

Accepted name: cholestanetriol 26-monooxygenase

Reaction: 5β-cholestane-3α,7α,12α-triol + 6 reduced adrenodoxin + 6 H+ + 3 O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 6 oxidized adrenodoxin + 4 H2O (overall reaction)
(1a) 5β-cholestane-3α,7α,12α-triol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 oxidized adrenodoxin + H2O
(1b) (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 oxidized adrenodoxin + 2 H2O
(1c) (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 2 oxidized adrenodoxin + H2O

For diagram of reaction click here.

Other name(s): 5β-cholestane-3α,7α,12α-triol 26-hydroxylase; 5β-cholestane-3α,7α,12α-triol hydroxylase; cholestanetriol 26-hydroxylase; sterol 27-hydroxylase; sterol 26-hydroxylase; cholesterol 27-hydroxylase; CYP27A; CYP27A1; cytochrome P450 27A1'

Systematic name: 5β-cholestane-3α,7α,12α-triol,adrenodoxin:oxygen oxidoreductase (26-hydroxylating)

Comments: This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3β,7α-diol, 7α-hydroxycholest-4-en-3-one, and 5β-cholestane-3α,7α-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Masui, T., Herman, R. and Staple, E. The oxidation of 5β-cholestane-3α,7α,12α,26-tetraol to 5β-cholestane-3α,7α,12α-triol-26-oic acid via 5β-cholestane-3α,7α,12α-triol-26-al by rat liver. Biochim. Biophys. Acta 117 (1966) 266-268. [PMID: 5914340]

2. Okuda, K. and Hoshita, N. Oxidation of 5β-cholestane-3α,7α,12α-triol by rat-liver mitochondria. Biochim. Biophys. Acta 164 (1968) 381-388. [PMID: 4388637]

3. Wikvall, K. Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C27-steroids. J. Biol. Chem. 259 (1984) 3800-3804. [PMID: 6423637]

4. Andersson, S., Davis, D.L., Dahlbäck, H., Jörnvall, H. and Russell, D.W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J. Biol. Chem. 264 (1989) 8222-8229. [PMID: 2722778]

5. Dahlback, H. and Holmberg, I. Oxidation of 5β-cholestane-3α,7α,12α-triol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid by cytochrome P-45026 from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 167 (1990) 391-395. [PMID: 2322231]

6. Holmberg-Betsholtz, I., Lund, E., Björkhem, I. and Wikvall, K. Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5β-cholestane-3α,7α,12α,27-tetrol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid. J. Biol. Chem. 268 (1993) 11079-11085. [PMID: 8496170]

7. Pikuleva, I.A., Babiker, A., Waterman, M.R. and Bjorkhem, I. Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways. J. Biol. Chem. 273 (1998) 18153-18160. [PMID: 9660774]

8. Furster, C., Bergman, T. and Wikvall, K. Biochemical characterization of a truncated form of CYP27A purified from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 263 (1999) 663-666. [PMID: 10512735]

9. Pikuleva, I.A., Puchkaev, A. and Björkhem, I. Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1. Biochemistry 40 (2001) 7621-7629. [PMID: 11412116]

[EC 1.14.15.15 created 1976 as EC 1.14.13.15, modified 2005, modified 2012, transferred 2016 to EC 1.14.15.15]

EC 1.14.15.16

Accepted name: vitamin D3 24-hydroxylase

Reaction: (1) calcitriol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitetrol + 2 oxidized adrenodoxin + H2O
(2) calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = secalciferol + 2 oxidized adrenodoxin + H2O

For diagram of reaction click here.

Glossary: calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D3 = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol
calcitetrol = 1α,24R,25-trihydroxyvitamin D3 = (1S,3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-1,3,24,25-tetrol
secalciferol = (24R)-24,25-dihydroxycalciol = 24R,25-dihydroxyvitamin D3 = (3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-3,24,25-triol

Other name(s): CYP24A1

Systematic name: calcitriol,adrenodoxin:oxygen oxidoreductase (24-hydroxylating)

Comments: This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. The enzyme can perform up to 6 rounds of hydroxylation of the substrate calcitriol leading to calcitroic acid. The human enzyme also shows 23-hydroxylating activity leading to 1,25 dihydroxyvitamin D3-26,23-lactone as end product while the mouse and rat enzymes do not. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Masuda, S., Strugnell, S.A., Knutson, J.C., St-Arnaud, R. and Jones, G. Evidence for the activation of 1α-hydroxyvitamin D2 by 25-hydroxyvitamin D-24-hydroxylase: delineation of pathways involving 1α,24-dihydroxyvitamin D2 and 1α,25-dihydroxyvitamin D2. Biochim. Biophys. Acta 1761 (2006) 221-234. [PMID: 16516540]

2. Hamamoto, H., Kusudo, T., Urushino, N., Masuno, H., Yamamoto, K., Yamada, S., Kamakura, M., Ohta, M., Inouye, K. and Sakaki, T. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol. Pharmacol. 70 (2006) 120-128. [PMID: 16617161]

3. Sakaki, T., Kagawa, N., Yamamoto, K. and Inouye, K. Metabolism of vitamin D3 by cytochromes P450. Front. Biosci. 10 (2005) 119-134. [PMID: 15574355]

4. Prosser, D.E., Kaufmann, M., O'Leary, B., Byford, V. and Jones, G. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1α,25-(OH)2D3-26,23-lactone. Proc. Natl. Acad. Sci. USA 104 (2007) 12673-12678. [PMID: 17646648]

5. Kusudo, T., Sakaki, T., Abe, D., Fujishima, T., Kittaka, A., Takayama, H., Hatakeyama, S., Ohta, M. and Inouye, K. Metabolism of A-ring diastereomers of 1α,25-dihydroxyvitamin D3 by CYP24A1. Biochem. Biophys. Res. Commun. 321 (2004) 774-782. [PMID: 15358094]

6. Sawada, N., Kusudo, T., Sakaki, T., Hatakeyama, S., Hanada, M., Abe, D., Kamao, M., Okano, T., Ohta, M. and Inouye, K. Novel metabolism of 1α,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1. Biochemistry 43 (2004) 4530-4537. [PMID: 15078099]

7. Prosser, D.E. and Jones, G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 29 (2004) 664-673. [PMID: 15544953]

[EC 1.14.15.16 created 2011 as EC 1.14.13.126, transferred 2016 to EC 1.14.15.16]

EC 1.14.15.17

Accepted name: pheophorbide-a oxygenase

Reaction: pheophorbide a + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = red chlorophyll catabolite + 2 oxidized ferredoxin [iron-sulfur] cluster (overall reaction)
(1a) pheophorbide a + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = epoxypheophorbide a + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) epoxypheophorbide a + H2O = red chlorophyll catabolite (spontaneous)

For diagram of reaction click here.

Glossary: red chlorophyll catabolite = RCC = (7S,8S,101R)-8-(2-carboxyethyl)-8,23-dihydro-17-ethyl-19-formyl-101-(methoxycarbonyl)-3,7,13,18-tetramethyl-2-vinyl-7H-10,12-ethanobiladiene-ab-1,102(21H)-dione

Other name(s): pheide a monooxygenase; pheide a oxygenase; PaO; PAO

Systematic name: pheophorbide-a,ferredoxin:oxygen oxidoreductase (biladiene-forming)

Comments: This enzyme catalyses a key reaction in chlorophyll degradation, which occurs during leaf senescence and fruit ripening in higher plants. The enzyme from Arabidopsis contains a Rieske-type iron-sulfur cluster [2] and requires reduced ferredoxin, which is generated either by NADPH through the pentose-phosphate pathway or by the action of photosystem I [4]. While still attached to this enzyme, the product is rapidly converted into primary fluorescent chlorophyll catabolite by the action of EC 1.3.7.12, red chlorophyll catabolite reductase [2,6]. Pheophorbide b acts as an inhibitor. In 18O2 labelling experiments, only the aldehyde oxygen is labelled, suggesting that the other oxygen atom may originate from H2O [1].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Hörtensteiner, S., Wüthrich, K.L., Matile, P., Ongania, K.H. and Kräutler, B. The key step in chlorophyll breakdown in higher plants. Cleavage of pheophorbide a macrocycle by a monooxygenase. J. Biol. Chem. 273 (1998) 15335-15339. [PMID: 9624113]

2. Pružinská, A., Tanner, G., Anders, I., Roca, M. and Hörtensteiner, S. Chlorophyll breakdown: pheophorbide a oxygenase is a Rieske-type iron-sulfur protein, encoded by the accelerated cell death 1 gene. Proc. Natl. Acad. Sci. USA 100 (2003) 15259-15264. [PMID: 14657372]

3. Chung, D.W., Pružinská, A., Hörtensteiner, S. and Ort, D.R. The role of pheophorbide a oxygenase expression and activity in the canola green seed problem. Plant Physiol. 142 (2006) 88-97. [PMID: 16844830]

4. Rodoni, S., Mühlecker, W., Anderl, M., Kräutler, B., Moser, D., Thomas, H., Matile, P. and Hörtensteiner, S. Chlorophyll breakdown in senescent chloroplasts. Cleavage of pheophorbide a in two enzymic steps. Plant Physiol. 115 (1997) 669-676. [PMID: 12223835]

5. Hörtensteiner, S. Chlorophyll degradation during senescence. Annu. Rev. Plant Biol. 57 (2006) 55-77. [PMID: 16669755]

6. Pružinská, A., Anders, I., Aubry, S., Schenk, N., Tapernoux-Lüthi, E., Müller, T., Kräutler, B. and Hörtensteiner, S. In vivo participation of red chlorophyll catabolite reductase in chlorophyll breakdown. Plant Cell 19 (2007) 369-387. [PMID: 17237353]

[EC 1.14.15.17 created 2007 as EC 1.14.12.20, transferred 2016 to EC 1.14.15.17]

EC 1.14.15.18

Accepted name: calcidiol 1-monooxygenase

Reaction: calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitriol + 2 oxidized adrenodoxin + H2O

For diagram of reaction click here.

Glossary: calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D3 = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol

Other name(s): 25-hydroxycholecalciferol 1-hydroxylase; 25-hydroxycholecalciferol 1-monooxygenase; 1-hydroxylase-25-hydroxyvitamin D3; 25-hydroxy D3-1α-hydroxylase; 25-hydroxycholecalciferol 1α-hydroxylase; 25-hydroxyvitamin D3 1α-hydroxylase

Systematic name: calcidiol,adrenodoxin:oxygen oxidoreductase (1-hydroxylating)

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Gray, R.W., Omdahl, J.L., Ghazarian, J.G. and De Luca, H.F. 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties. J. Biol. Chem. 247 (1972) 7528-7532. [PMID: 4404596]

[EC 1.14.15.18 created 1976 as EC 1.14.13.13, transferred 2016 to EC 1.14.15.18]

EC 1.14.15.19

Accepted name: C-19 steroid 1α-hydroxylase

Reaction: testosterone + 2 reduced ferredoxin [iron-sulfur] cluster + O2 + 2 H+ = 1α-hydroxytestosterone + H2O + 2 oxidized ferredoxin [iron-sulfur] cluster

Other name(s): CYP260A1

Systematic name: testosterone,reduced-ferredoxin:oxygen oxidoreductase (1α-hydroxylating)

Comments: The enzyme, characterized from the bacterium Sorangium cellulosum, is a class I cytochrome P-450, and uses ferredoxin as its electron donor [1]. It was shown to act on several C-19 steroid substrates, including testosterone, androstenedione, testosterone-acetate and 11-oxoandrostenedione [2].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Ewen, K.M., Hannemann, F., Khatri, Y., Perlova, O., Kappl, R., Krug, D., Huttermann, J., Muller, R. and Bernhardt, R. Genome mining in Sorangium cellulosum So ce56: identification and characterization of the homologous electron transfer proteins of a myxobacterial cytochrome P450. J. Biol. Chem. 284 (2009) 28590-28598. [PMID: 19696019]

2. Khatri, Y., Ringle, M., Lisurek, M., von Kries, J.P., Zapp, J. and Bernhardt, R. Substrate hunting for the myxobacterial CYP260A1 revealed new 1α-hydroxylated products from C-19 steroids. Chembiochem 17 (2016) 90-101. [PMID: 26478560]

[EC 1.14.15.19 created 2016]

EC 1.14.15.20

Accepted name: heme oxygenase (biliverdin-producing, ferredoxin)

Reaction: protoheme + 6 reduced ferredoxin [iron-sulfur] cluster + 3 O2 + 6 H+ = biliverdin + Fe2+ + CO + 6 oxidized ferredoxin [iron-sulfur] cluster + 3 H2O

For diagram of reaction click here.

Other name(s): HO1 (gene name); HY1 (gene name); HO3 (gene name); HO4 (gene name); pbsA1 (gene name)

Systematic name: protoheme,reduced ferredoxin:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)

Comments: The enzyme, found in plants, algae, and cyanobacteria, participates in the biosynthesis of phytochromobilin and phytobilins. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules. The third oxygen molecule provides the oxygen atom that converts the α-carbon to CO. Unlike this enzyme, which uses ferredoxin as its electron donor, the electron source for the related mammalian enzyme (EC 1.14.14.18) is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Montgomery, B.L. and Lagarias, J.C. Phytochrome ancestry: sensors of bilins and light. Trends Plant Sci 7 (2002) 357-366. [PMID: 12167331]

2. Sugishima, M., Migita, C.T., Zhang, X., Yoshida, T. and Fukuyama, K. Crystal structure of heme oxygenase-1 from cyanobacterium Synechocystis sp. PCC 6803 in complex with heme. Eur. J. Biochem. 271 (2004) 4517-4525. [PMID: 15560792]

3. Dammeyer, T. and Frankenberg-Dinkel, N. Function and distribution of bilin biosynthesis enzymes in photosynthetic organisms. Photochem Photobiol Sci 7 (2008) 1121-1130. [PMID: 18846276]

[EC 1.14.15.20 created 2016]

EC 1.14.15.21

Accepted name: zeaxanthin epoxidase

Reaction: zeaxanthin + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H+ + 2 O2 = violaxanthin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O (overall reaction)
(1a) zeaxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = antheraxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) antheraxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = violaxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

For diagram of reaction click here.

Other name(s): Zea-epoxidase

Systematic name: zeaxanthin,reduced ferredoxin:oxygen oxidoreductase

Comments: A flavoprotein (FAD) that is active under conditions of low light. Along with EC 1.23.5.1, violaxanthin de-epoxidase, this enzyme forms part of the xanthophyll (or violaxanthin) cycle, which is involved in protecting the plant against damage by excess light. It will also epoxidize lutein in some higher-plant species.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Buch, K., Stransky, H. and Hager, A. FAD is a further essential cofactor of the NAD(P)H and O2-dependent zeaxanthin-epoxidase. FEBS Lett. 376 (1995) 45-48. [PMID: 8521963]

2. Bugos, R.C., Hieber, A.D. and Yamamoto, H.Y. Xanthophyll cycle enzymes are members of the lipocalin family, the first identified from plants. J. Biol. Chem. 273 (1998) 15321-15324. [PMID: 9624110]

3. Thompson, A.J., Jackson, A.C., Parker, R.A., Morpeth, D.R., Burbidge, A. and Taylor, I.B. Abscisic acid biosynthesis in tomato: regulation of zeaxanthin epoxidase and 9-cis-epoxycarotenoid dioxygenase mRNAs by light/dark cycles, water stress and abscisic acid. Plant Mol. Biol. 42 (2000) 833-845. [PMID: 10890531]

4. Hieber, A.D., Bugos, R.C. and Yamamoto, H.Y. Plant lipocalins: violaxanthin de-epoxidase and zeaxanthin epoxidase. Biochim. Biophys. Acta 1482 (2000) 84-91. [PMID: 11058750]

5. Frommolt, R., Goss, R. and Wilhelm, C. The de-epoxidase and epoxidase reactions of Mantoniella squamata (Prasinophyceae) exhibit different substrate-specific reaction kinetics compared to spinach. Planta 213 (2001) 446-456. [PMID: 11506368]

6. Frommolt, R., Goss, R. and Wilhelm, C. (Erratum Report.) The de-epoxidase and epoxidase reactions of Mantoniella squamata (Prasinophyceae) exhibit different substrate-specific reaction kinetics compared to spinach. Planta 213 (2001) 492. [PMID: 11506368]

7. Matsubara, S., Morosinotto, T., Bassi, R., Christian, A.L., Fischer-Schliebs, E., Luttge, U., Orthen, B., Franco, A.C., Scarano, F.R., Forster, B., Pogson, B.J. and Osmond, C.B. Occurrence of the lutein-epoxide cycle in mistletoes of the Loranthaceae and Viscaceae. Planta 217 (2003) 868-879. [PMID: 12844265]

[EC 1.14.15.21 created 2005 as EC 1.14.13.90, transferred 2016 to EC 1.14.15.21]

EC 1.14.15.22

Accepted name: vitamin D 1,25-hydroxylase

Reaction: (1) calciol + O2 + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ = calcidiol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(2) calcidiol + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = calcitriol + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Glossary: calciol = cholecalciferol = vitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol
calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D3 = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol

Other name(s): CYP105A1; Streptomyces griseolus cytochrome P450SU-1

Systematic name: calciol,ferredoxin:oxygen oxidoreductase (1,25-hydroxylating)

Comments: A P-450 (heme-thiolate) enzyme found in the bacterium Streptomyces griseolus. cf. EC 1.14.14.24, vitamin D 25-hydroxylase and EC 1.14.15.18, calcidiol 1-monooxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Sawada, N., Sakaki, T., Yoneda, S., Kusudo, T., Shinkyo, R., Ohta, M. and Inouye, K. Conversion of vitamin D3 to 1α,25-dihydroxyvitamin D3 by Streptomyces griseolus cytochrome P450SU-1. Biochem. Biophys. Res. Commun. 320 (2004) 156-164. [PMID: 15207715]

2. Sugimoto, H., Shinkyo, R., Hayashi, K., Yoneda, S., Yamada, M., Kamakura, M., Ikushiro, S., Shiro, Y. and Sakaki, T. Crystal structure of CYP105A1 (P450SU-1) in complex with 1α,25-dihydroxyvitamin D3. Biochemistry 47 (2008) 4017-4027. [PMID: 18314962]

[EC 1.14.15.22 created 2016]

EC 1.14.15.23

Accepted name: chloroacetanilide N-alkylformylase

Reaction: butachlor + 2 reduced ferredoxin [iron-sulfur] cluster + O2 = 2-chloro-N-(2,6-diethylphenyl)acetamide + butyl formate + 2 reduced ferredoxin [iron-sulfur] cluster + H2O

Glossary: butachlor = N-(butoxymethyl)-2-chloro-N-(2,6-diethylphenyl)acetamide
acetochlor = N-(ethoxymethyl)-2-chloro-N-(2-ethyl,6-methylphenyl)acetamide
alachlor = N-(methoxymethyl)-2-chloro-N-(2,6-diethylphenyl)acetamide

Other name(s): cndA (gene name)

Systematic name: butachlor,ferredoxin:oxygen oxidoreductase (butyl formate-releasing)

Comments: The enzyme, characterized from the bacterium Sphingomonas sp. DC-6, initiates the degradation of several chloroacetanilide herbicides, including alachlor, acetochlor, and butachlor. The enzyme is a Rieske non-heme iron oxygenase, and requires a ferredoxin and EC 1.18.1.3, ferredoxin-NAD+ reductase, for activity.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Chen, Q., Wang, C.H., Deng, S.K., Wu, Y.D., Li, Y., Yao, L., Jiang, J.D., Yan, X., He, J. and Li, S.P. Novel three-component Rieske non-heme iron oxygenase system catalyzing the N-dealkylation of chloroacetanilide herbicides in sphingomonads DC-6 and DC-2. Appl. Environ. Microbiol. 80 (2014) 5078-5085. [PMID: 24928877]

[EC 1.14.15.23 created 2017]


EC 1.14.16 With reduced pteridine as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.16.1 phenylalanine 4-monooxygenase
EC 1.14.16.2 tyrosine 3-monooxygenase
EC 1.14.16.3 anthranilate 3-monooxygenase
EC 1.14.16.4 tryptophan 5-monooxygenase
EC 1.14.16.5 alkylglycerol monooxygenase
EC 1.14.16.6 mandelate 4-monooxygenase

EC 1.14.16.7 phenylalanine 3-monooxygenase


EC 1.14.16.1

Accepted name: phenylalanine 4-monooxygenase

Reaction: L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin

For diagram click here and here also for mechanism.

Other name(s): phenylalaninase; phenylalanine 4-hydroxylase; phenylalanine hydroxylase

Systematic name: L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, 6,7-dihydropteridine reductase, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9029-73-6

References:

1. Guroff, G. and Rhoads, C.A. Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a). Nature of the cofactor. J. Biol. Chem. 244 (1969) 142-146. [PMID: 5773277]

2. Kaufman, S. Studies on the mechanism of the enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 234 (1959) 2677-2682.

3. Mitoma, C. Studies on partially purified phenylalanine hydroxylase. Arch. Biochem. Biophys. 60 (1956) 476-484.

4. Udenfriend, S. and Cooper, J.R. The enzymic conversion of phenylalanine to tyrosine. J. Biol. Chem. 194 (1952) 503-511.

5. Carr, R.T., Balasubramanian, S., Hawkins, P.C. and Benkovic, S.J. Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase. Biochemistry 34 (1995) 7525-7532. [PMID: 7779797]

6. Andersen, O.A., Flatmark, T. and Hough, E. High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J. Mol. Biol. 314 (2001) 266-278. [PMID: 11718561]

7. Erlandsen, H., Kim, J.Y., Patch, M.G., Han, A., Volner, A., Abu-Omar, M.M. and Stevens, R.C. Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates. J. Mol. Biol. 320 (2002) 645-661. [PMID: 12096915]

[EC 1.14.16.1 created 1961 as EC 1.99.1.2, transferred 1965 to EC 1.14.3.1, transferred 1972 to EC 1.14.16.1, modified 2002, modified 2003]

EC 1.14.16.2

Accepted name: tyrosine 3-monooxygenase

Reaction: L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin

For diagram click here and here.

Glossary: L-dopa = 3,4-dihydroxy-L-phenylalanine

Other name(s): L-tyrosine hydroxylase; tyrosine 3-hydroxylase; tyrosine hydroxylase

Systematic name: L-tyrosine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by EC 2.7.11.27, [acetyl-CoA caboxylase]kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9036-22-0

References:

1. El Mestikawy, S., Glowinski, J. and Hamon, M. Tyrosine hydroxylase activation in depolarized dopaminergic terminals -involvement of Ca2+-dependent phosphorylation. Nature (Lond.) 302 (1983) 830-832. [PMID: 6133218]

2. Ikeda, M., Levitt, M. and Udenfriend, S. Phenylalanine as substrate and inhibitor of tyrosine hydroxylase. Arch. Biochem. Biophys. 120 (1967) 420-427. [PMID: 6033458]

3. Nagatsu, T., Levitt, M. and Udenfriend, S. Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239 (1964) 2910-2917.

4. Pigeon, D., Drissi-Daoudi, R., Gros, F. and Thibault, J. Copurification of tyrosine-hydroxylase from rat pheochromocytoma, with a protein-kinase activity. C.R. Acad. Sci. Paris, Ser. 3, 302 (1986) 435-438. [PMID: 2872947]

5. Goodwill, K.E., Sabatier, C., Marks, C., Raag, R., Fitzpatrick, P.F. and Stevens, R.C. Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases. Nat. Struct. Biol. 4 (1997) 578-585. [PMID: 9228951]

[EC 1.14.16.2 created 1972, modified 2003]

EC 1.14.16.3

Accepted name: anthranilate 3-monooxygenase

Reaction: anthranilate + tetrahydrobiopterin + O2 = 3-hydroxyanthranilate + dihydrobiopterin + H2O

Other name(s): anthranilate 3-hydroxylase; anthranilate hydroxylase; anthranilic hydroxylase; anthranilic acid hydroxylase

Systematic name: anthranilate,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe2+.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-79-4

References:

1. Jequier, E., Robinson, B.S., Lovenberg, W. and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18 (1969) 1071-1081. [PMID: 5789774]

2. Nair, P.M. and Vaidyanathan, C.S. Anthranilic acid hydroxylase from Tecoma stans. Biochim. Biophys. Acta 110 (1965) 521-531.

[EC 1.14.16.3 created 1972]

EC 1.14.16.4

Accepted name: tryptophan 5-monooxygenase

Reaction: L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin

For diagram click here.

Other name(s): L-tryptophan hydroxylase; indoleacetic acid-5-hydroxylase; tryptophan 5-hydroxylase; tryptophan hydroxylase

Systematic name: L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)

Comments: The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34 (6,7-dihydropteridine reductase), or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9037-21-2

References:

1. Friedman, P.A., Kappelman, A.H. and Kaufman, S. Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 247 (1972) 4165-4173. [PMID: 4402511]

2. Hamon, M., Bourgoin, S., Artaud, F. and Glowinski, J. The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium. J. Neurochem. 33 (1979) 1031-1042. [PMID: 315449]

3. Ichiyama, A., Nakamura, S., Nishizuka, Y. and Hayaishi, O. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J. Biol. Chem. 245 (1970) 1699-1709. [PMID: 5309585]

4. Jequier, E., Robinson, B.S., Lovenberg, W. and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 18 (1969) 1071-1081. [PMID: 5789774]

5. Wang, L., Erlandsen, H., Haavik, J., Knappskog, P.M. and Stevens, R.C. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry 41 (2002) 12569-12574. [PMID: 12379098]

[EC 1.14.16.4 created 1972, modified 2003]

EC 1.14.16.5

Accepted name: alkylglycerol monooxygenase

Reaction: 1-alkyl-sn-glycerol + tetrahydrobiopterin + O2 = 1-O-alkyl-sn-glycerol + dihydrobiopterin + H2O

Other name(s): glyceryl-ether monooxygenase; glyceryl-ether cleaving enzyme; alkylglycerol monooxygenase; glyceryl ether oxygenase; glyceryl etherase; O-alkylglycerol monooxygenase

Systematic name: 1-alkyl-sn-glycerol,tetrahydrobiopterin:oxygen oxidoreductase

Comments: The enzyme cleaves alkylglycerols, but does not cleave alkenylglycerols (plasmalogens). Requires reduced glutathione and phospholipids for full activity. The product spontaneously breaks down to form a fatty aldehyde and glycerol.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37256-82-9

References:

1. Ishibashi, T. and Imai, Y. Solubilization and partial characterization of alkylglycerol monooxygenase from rat liver microsomes. Eur. J. Biochem. 132 (1983) 23-27. [PMID: 6840084]

2. Pfleger, E.C., Piantadosi, C. and Snyder, F. The biocleavage of isomeric glyceryl ethers by soluble liver enzymes in a variety of species. Biochim. Biophys. Acta 144 (1967) 633-648. [PMID: 4383918]

3. Snyder, F., Malone, B. and Piantadosi, C. Tetrahydropteridine-dependent cleavage enzyme for O-alkyl lipids: substrate specificity. Biochim. Biophys. Acta 316 (1973) 259-265. [PMID: 4355017]

4. Soodsma, J.F., Piantadosi, C. and Snyder, F. Partial characterization of the alkylglycerol cleavage enzyme system of rat liver. J. Biol. Chem. 247 (1972) 3923-3929. [PMID: 4402391]

5. Tietz, A., Lindberg, M. and Kennedy, E.P. A new pteridine-requiring enzyme system for the oxidation of glyceryl ethers. J. Biol. Chem. 239 (1964) 4081-4090. [PMID: 14247652]

6. Taguchi, H. and Armarego, W.L. Glyceryl-ether monooxygenase [EC 1.14.16.5]. A microsomal enzyme of ether lipid metabolism. Med. Res. Rev. 18 (1998) 43-89. [PMID: 9436181]

[EC 1.14.16.5 created 1972 as EC 1.14.99.17, transferred 1976 to EC 1.14.16.5, modified 2010]

EC 1.14.16.6

Accepted name: mandelate 4-monooxygenase

Reaction: (S)-2-hydroxy-2-phenylacetate + tetrahydrobiopterin + O2 = (S)-4-hydroxymandelate + dihydrobiopterin + H2O

Glossary: (S)-4-hydroxymandelate = (S)-2-hydroxy-2-(4-hydroxyphenyl)acetate

Other name(s): L-mandelate 4-hydroxylase; mandelic acid 4-hydroxylase

Systematic name: (S)-2-hydroxy-2-phenylacetate,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)

Comments: Requires Fe2+.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 39459-82-0

References:

1. Bhat, S.G. and Vaidyanathan, C.S. Purifications and properties of L-mandelate-4-hydroxylase from Pseudomonas convexa. Arch. Biochem. Biophys. 176 (1976) 314-323. [PMID: 9909]

[EC 1.14.16.6 created 1984]

EC 1.14.16.7

Accepted name: phenylalanine 3-monooxygenase

Reaction: L-phenylalanine + tetrahydrobiopterin + O2 = 3-hydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin

Glossary: 3-hydroxy-L-phenylalanine = meta-L-tyrosine = 3-(3-hydroxyphenyl)-L-alanine

Other name(s): PacX; phenylalanine 3-hydroxylase

Systematic name: L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating)

Comments: The enzyme from the bacterium Streptomyces coeruleorubidus forms 3-hydroxy-L-phenylalanine (i.e. m-L-tyrosine), which is one of the building blocks in the biosynthesis of the uridyl peptide antibiotics pacidamycins.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:

References:

1. Zhang, W., Ames, B.D. and Walsh, C.T. Identification of phenylalanine 3-hydroxylase for meta-tyrosine biosynthesis. Biochemistry 50 (2011) 5401-5403. [PMID: 21615132]

[EC 1.14.16.7 created 2014]


EC 1.14.17 With ascorbate as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.17.1 dopamine β-monooxygenase
EC 1.14.17.2 deleted, included in EC 1.14.18.1
EC 1.14.17.3 peptidylglycine monooxygenase
EC 1.14.17.4 aminocyclopropanecarboxylate oxidase


EC 1.14.17.1

Accepted name: dopamine β-monooxygenase

Reaction: dopamine + ascorbate + O2 = noradrenaline + dehydroascorbate + H2O

For diagram click here.

Glossary: dopamine = 4-(2-aminoethyl)benzene-1,2-diol

Other name(s): dopamine β-hydroxylase; MDBH (membrane-associated dopamine β-monooxygenase); SDBH (soluble dopamine β-monooxygenase); dopamine-B-hydroxylase; oxygenase, dopamine β-mono-; 3,4-dihydroxyphenethylamine β-oxidase; 4-(2-aminoethyl)pyrocatechol β-oxidase; dopa β-hydroxylase; dopamine β-oxidase; dopamine hydroxylase; phenylamine β-hydroxylase; (3,4-dihydroxyphenethylamine)β-mono-oxygenase; DβM

Systematic name: 3,4-dihydroxyphenethylamine,ascorbate:oxygen oxidoreductase (β-hydroxylating)

Comments: A copper protein. Stimulated by fumarate. Formerly EC 1.14.2.1.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9013-38-1

References:

1. Friedman, S. and Kaufman, S. 3,4-Dihydroxyphenylethylamine β-hydroxylase. Physical properties, copper content, and role of copper in the catalytic activity. J. Biol. Chem. 240 (1965) 4763-4773. [PMID: 5846992]

2. Levin, E.Y., Levenberg, B. and Kaufman, S. The enzymatic conversion of 3,4-dihydroxyphenylethylamine to norepinephrine. J. Biol. Chem. 235 (1960) 2080-2086.

[EC 1.14.17.1 created 1965 as EC 1.14.2.1, transferred 1972 to EC 1.14.17.1]

[EC 1.14.17.2 Deleted entry: 4-coumarate 3-monooxygenase. Now included with EC 1.14.18.1 monophenol monooxygenase (EC 1.14.17.2 created 1972, deleted 1984)]

EC 1.14.17.3

Accepted name: peptidylglycine monooxygenase

Reaction: peptidylglycine + ascorbate + O2 = peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O

Other name(s): peptidylglycine 2-hydroxylase; peptidyl α-amidating enzyme; peptide-α-amide synthetase; synthase, peptide α-amide; peptide α-amidating enzyme; peptide α-amide synthase; peptidylglycine α-hydroxylase; peptidylglycine α-amidating monooxygenase; PAM-A; PAM-B; PAM

Systematic name: peptidylglycine,ascorbate:oxygen oxidoreductase (2-hydroxylating)

Comments: A copper protein. Peptidylglycines with a neutral amino acid residue in the penultimate position are the best substrates for the enzyme. The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide, a reaction catalysed by EC 4.3.2.5 peptidylamidoglycolate lyase. Involved in the final step of biosynthesis of α-melanotropin and related biologically active peptides.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 90597-47-0

References:

1. Bradbury, A.F., Finnie, M.D.A. and Smyth, D.G. Mechanism of C-terminal amide formation by pituitary enzymes. Nature (Lond.) 298 (1982) 686-688. [PMID: 7099265]

2. Bradbury, A.F. and Smyth, D.G. Enzyme-catalysed peptide amidation. Isolation of a stable intermediate formed by reaction of the amidating enzyme with an imino acid. Eur. J. Biochem. 169 (1987) 579-584. [PMID: 3691506]

3. Glembotski, C.G.Further characterization of the peptidyl α-amidating enzyme in rat anterior pituitary secretory granules. Arch. Biochem. Biophys. 241 (1985) 673-683. [PMID: 2994573]

4. Katopodis, A.G., Ping, D. and May, S.W. A novel enzyme from bovine neurointermediate pituitary catalyzes dealkylation of α-hydroxyglycine derivatives, thereby functioning sequentially with peptidylglycine α-amidating monooxygenase in peptide amidation. Biochemistry 29 (1990) 6115-6120. [PMID: 2207061]

5.Murthy, A.S.N., Keutmann, H.T. and Eipper, B.A. Further characterization of peptidylglycine α-amidating monooxygenase from bovine neurointermediate pituitary. Mol. Endocrinol. 1 (1987) 290-299. [PMID: 3453894]

6.Murthy, A.S.N., Mains, R.E. and Eipper, B.A. Purification and characterization of peptidylglycine α-amidating monooxygenase from bovine neurointermediate pituitary. J.Biol. Chem. 261 (1986) 1815-1822. [PMID: 3944110]

[EC 1.14.17.3 created 1989]

EC 1.14.17.4

Accepted name: aminocyclopropanecarboxylate oxidase

Reaction: 1-aminocyclopropane-1-carboxylate + ascorbate + O2 = ethylene + cyanide + dehydroascorbate + CO2 + 2 H2O

For diagram click here.

Other name(s): ACC oxidase; ethylene-forming enzyme

Systematic name: 1-aminocyclopropane-1-carboxylate oxygenase (ethylene-forming)

Comments: A nonheme iron enzyme. Requires CO2 for activity. In the enzyme from plants, the ethylene has signalling functions such as stimulation of fruit-ripening.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 98668-53-2

References:

1. Zhang, Z.H., Schofield, C.J., Baldwin, J.E., Thomas, P. and John, P. Expression, purification and characterization of 1-aminocyclopropane-1-carboxylate oxidase from tomato in Escherichia coli. Biochem. J. 307 (1995) 77-85. [PMID: 7717997]

2. Zhang, Z.H., Barlow, J.N., Baldwin, J.E. and Schofield, C.J. Metal-catalyzed oxidation and mutagenesis studies on the iron(II) binding site of 1-aminocyclopropane-1-carboxylate oxidase. Biochemistry 36 (1997) 15999-16007. [PMID: 9398335]

3. Pirrung, M.C. Ethylene biosynthesis from 1-aminocyclopropanecarboxylic acid. Acc. Chem. Res. 32 (1999) 711-718.

4. Charng, Y., Chou, S.J., Jiaang, W.T., Chen, S.T. and Yang, S.F. The catalytic mechanism of 1-aminocyclopropane-1-carboxylic acid oxidase. Arch. Biochem. Biophys. 385 (2001) 179-185. [PMID: 11361015]

5. Thrower, J.S., Blalock, R. and Klinman, J.P. Steady-state kinetics of substrate binding and iron release in tomato ACC oxidase. Biochemistry 40 (2001) 9717-9724. [PMID: 11583172]

[EC 1.14.17.4 created 2003]


EC 1.14.18 With another compound as one donor, and incorporation of one atom of oxygen

Contents

EC 1.14.18.1 tyrosinase
EC 1.14.18.2 CMP-N-acetylneuraminate monooxygenase
EC 1.14.18.3 methane monooxygenase (particulate)
EC 1.14.18.4 phosphatidylcholine 12-monooxygenase
EC 1.14.18.5 sphingolipid C4-monooxygenase
EC 1.14.18.6 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase
EC 1.14.18.7 dihydroceramide fatty acyl 2-hydroxylase
EC 1.14.18.8 7α-hydroxycholest-4-en-3-one 12α-hydroxylase
EC 1.14.18.9 methylsterol monooxygenase

EC 1.14.18.1

Accepted name: tyrosinase

Reaction: (1) L-tyrosine + O2 = dopaquinone + H2O (overall reaction)
(1a) L-tyrosine + ½ O2 = L-dopa
(1b) L-dopa + ½ O2 = dopaquinone + H2O
(2) 2 L-dopa + O2 = 2 dopaquinone + 2 H2O

For diagram of reaction click here.

Other name(s): monophenol monooxygenase; phenolase; monophenol oxidase; cresolase; monophenolase; tyrosine-dopa oxidase; monophenol monooxidase; monophenol dihydroxyphenylalanine:oxygen oxidoreductase; N-acetyl-6-hydroxytryptophan oxidase; monophenol, dihydroxy-L-phenylalanine oxygen oxidoreductase; o-diphenol:O2 oxidoreductase; phenol oxidase

Systematic name: L-tyrosine,L-dopa:oxygen oxidoreductase

Comments: A type III copper protein found in a broad variety of bacteria, fungi, plants, insects, crustaceans, and mammals, which is involved in the synthesis of betalains and melanin. The enzyme, which is activated upon binding molecular oxygen, can catalyse both a monophenolase reaction cycle (reaction 1) or a diphenolase reaction cycle (reaction 2). During the monophenolase cycle, one of the bound oxygen atoms is transferred to a monophenol (such as L-tyrosine), generating an o-diphoenol intermediate, which is subsequently oxidized to an o-quinone and released, along with a water molecule. The enzyme remains in an inactive deoxy state, and is restored to the active oxy state by the binding of a new oxygen molecule. During the diphenolase cycle the enzyme binds an external diphenol molecule (such as L-dopa) and oxidizes it to an o-quinone that is released along with a water molecule, leaving the enzyme in the intermediate met state. The enzyme then binds a second diphenol molecule and repeats the process, ending in a deoxy state [7]. The second reaction is identical to that catalysed by the related enzyme catechol oxidase (EC 1.10.3.1). However, the latter can not catalyse the hydroxylation or monooxygenation of monophenols.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9002-10-2

References:

1. Dawson, C.R. and Tarpley, W.B. The copper oxidases. In: Sumner, J.B. and Myrbäck, K. (Eds), The Enzymes, 1st edn, vol. 2, Academic Press, New York, 1951, pp. 454-498.

2. Patil, S.S. and Zucker, M. Potato phenolases. Purification and properties. J. Biol. Chem. 240 (1965) 3938-3943. [PMID: 5842066]

3. Pomerantz, S.H. Separation, purification, and properties of two tyrosinases from hamster melanoma. J. Biol. Chem. 238 (1963) 2351-2357. [PMID: 13972077]

4. Robb, D.A. `Tyrosinase. In: Lontie, R. (Ed.), Copper Proteins and Copper Enzymes, vol. 2, CRC Press, Boca Raton, FL, 1984, pp. 207-240.

5. Sanchez-Ferrer, A., Rodriguez-Lopez, J.N., Garcia-Canovas, F. and Garcia-Carmona, F. Tyrosinase: a comprehensive review of its mechanism. Biochim. Biophys. Acta 1247 (1995) 1-11. [PMID: 7873577]

6. Steiner, U., Schliemann, W. and Strack, D. Assay for tyrosine hydroxylation activity of tyrosinase from betalain-forming plants and cell cultures. Anal. Biochem. 238 (1996) 72-75. [PMID: 8660589]

7. Rolff, M., Schottenheim, J., Decker, H. and Tuczek, F. Copper-O2 reactivity of tyrosinase models towards external monophenolic substrates: molecular mechanism and comparison with the enzyme. Chem Soc Rev 40 (2011) 4077-4098. [PMID: 21416076]

[EC 1.14.18.1 created 1972, modified 1976, modified 1980 (EC 1.14.17.2 created 1972, incorporated 1984), modified 2012]

EC 1.14.18.2

Accepted name: CMP-N-acetylneuraminate monooxygenase

Reaction: CMP-N-acetylneuraminate + 2 ferrocytochrome b5 + O2 + 2 H+ = CMP-N-glycoloylneuraminate + 2 ferricytochrome b5 + H2O

Other name(s): CMP-N-acetylneuraminic acid hydroxylase; CMP-Neu5Ac hydroxylase; cytidine monophosphoacetylneuraminate monooxygenase; N-acetylneuraminic monooxygenase; cytidine-5'-monophosphate-N-acetylneuraminic acid hydroxylase

Systematic name: CMP-N-acetylneuraminate,ferrocytochrome-b5:oxygen oxidoreductase (N-acetyl-hydroxylating)

Comments: This enzyme contains both a Rieske-type [2Fe-2S] cluster and a second iron site. The ferricytochrome b5 produced is reduced by NADH and cytochrome-b5 reductase (EC 1.6.2.2). The enzyme can be activated by Fe2+ or Fe3+.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 116036-67-0

References:

1. Shaw, L. and Schauer, R. The biosynthesis of N-glycoloylneuraminic acid occurs by hydroxylation of the CMP-glycoside of N-acetylneuraminic acid. Biol. Chem. Hoppe-Seyler 369 (1988) 477-486. [PMID: 3202954]

2. Kozutsumi, Y., Kawano, T., Yamakawa, T. and Suzuki, A. Participation of cytochrome b5 in CMP-N-acetylneuraminic acid hydroxylation in mouse liver cytosol. J. Biochem. (Tokyo) 109 (1990) 704-706.[PMID: 1964451]

3. Schneckenburger, P., Shaw, L. and Schauer, R. Purification, characterization and reconstitution of CMP-N-acetylneuraminate hydroxylase from mouse liver. Glycoconj. J. 11 (1994) 194-203. [PMID: 7841794]

4. Kawano, T., Koyama, S., Takematsu, H., Kozutsumi, Y., Kawasaki, H., Kawashima, S., Kawasaki, T. and Suzuki, A. Molecular cloning of cytidine monophospho-N-acetylneuraminic acid hydroxylase. Regulation of species- and tissue-specific expression of N-glycolylneuraminic acid. J. Biol. Chem. 270 (1995) 16458-16463. [PMID: 7608218]

5. Schlenzka, W., Shaw, L., Kelm, S., Schmidt, C.L., Bill, E., Trautwein, A.X., Lottspeich, F. and Schauer, R. CMP-N-acetylneuraminic acid hydroxylase: the first cytosolic Rieske iron-sulphur protein to be described in Eukarya. FEBS Lett. 385 (1996) 197-200. [PMID: 8647250]

[EC 1.14.18.2 created 1992 as EC 1.14.13.45, transferred 2003 to EC 1.14.18.2]

EC 1.14.18.3

Accepted name: methane monooxygenase (particulate)

Reaction: methane + quinol + O2 = methanol + quinone + H2O

Systematic name: methane,quinol:oxygen oxidoreductase

Comments: Contains copper. It is membrane-bound, in contrast to the soluble methane monooxygenase (EC 1.14.13.25).

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:

References:

1. Shiemke, A.K., Cook, S.A., Miley, T. and Singleton, P. Detergent solubilization of membrane-bound methane monooxygenase requires plastoquinol analogs as electron donors. Arch. Biochem. Biophys. 321 (1995) 421-428. [PMID: 7646068]

2. Basu, P., Katterle, B., Andersson, K.K. and Dalton, H. The membrane-associated form of methane mono-oxygenase from Methylococcus capsulatus (Bath) is a copper/iron protein. Biochem. J. 369 (2003) 417-427. [PMID: 12379148]

3. Kitmitto, A., Myronova, N., Basu, P. and Dalton, H. Characterization and structural analysis of an active particulate methane monooxygenase trimer from Methylococcus capsulatus (Bath). Biochemistry 44 (2005) 10954-10965. [PMID: 16101279]

4. Balasubramanian, R. and Rosenzweig, A.C. Structural and mechanistic insights into methane oxidation by particulate methane monooxygenase. Acc. Chem. Res. 40 (2007) 573-580. [PMID: 17444606]

[EC 1.14.18.3 created 2011]

EC 1.14.18.4

Accepted name: phosphatidylcholine 12-monooxygenase

Reaction: a 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine + 2 ferrocytochrome b5 + O2 + 2 H+ = a 1-acyl-2-[(12R)-12-hydroxyoleoyl]-sn-glycero-3-phosphocholine + 2 ferricytochrome b5 + H2O

Glossary: ricinoleic acid = (9Z,12R)-12-hydroxyoctadec-9-enoic acid

Other name(s): ricinoleic acid synthase; oleate Δ12-hydroxylase; oleate Δ12-monooxygenase

Systematic name: 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine,ferrocytochrome-b5:oxygen oxidoreductase (12-hydroxylating)

Comments: The enzyme, characterized from the plant Ricinus communis (castor bean), is involved in production of the 12-hydroxylated fatty acid ricinoleate. The enzyme, which shares sequence similarity with fatty-acyl desaturases, requires a cytochrome b5 as the electron donor.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Galliard, T. and Stumpf, P.K. Fat metabolism in higher plants. 30. Enzymatic synthesis of ricinoleic acid by a microsomal preparation from developing Ricinus communis seeds. J. Biol. Chem. 241 (1966) 5806-5812. [PMID: 4289003]

2. Moreau, R.A. and Stumpf, P.K. Recent studies of the enzymic-synthesis of ricinoleic acid by developing castor beans. Plant Physiol. 67 (1981) 672-676. [PMID: 16661734]

3. Smith, M.A., Jonsson, L., Stymne, S. and Stobart, K. Evidence for cytochrome b5 as an electron donor in ricinoleic acid biosynthesis in microsomal preparations from developing castor bean (Ricinus communis L.). Biochem. J. 287 (1992) 141-144. [PMID: 1417766]

4. Lin, J.T., McKeon, T.A., Goodrich-Tanrikulu, M. and Stafford, A.E. Characterization of oleoyl-12-hydroxylase in castor microsomes using the putative substrate, 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine. Lipids 31 (1996) 571-577. [PMID: 8784737]

5. Broun, P. and Somerville, C. Accumulation of ricinoleic, lesquerolic, and densipolic acids in seeds of transgenic Arabidopsis plants that express a fatty acyl hydroxylase cDNA from castor bean. Plant Physiol. 113 (1997) 933-942. [PMID: 9085577]

[EC 1.14.18.4 created 1984 as EC 1.14.13.26, transferred 2015 to EC 1.14.18.4]

EC 1.14.18.5

Accepted name: sphingolipid C4-monooxygenase

Reaction: a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4R)-4-hydroxysphinganine ceramide + 2 ferricytochrome b5 + H2O

Other name(s): sphinganine C4-monooxygenase; sphingolipid C4-hydroxylase; SUR2 (gene name); SBH1 (gene name); SBH2 (gene name); DEGS2 (gene name)

Systematic name: dihydroceramide,ferrocytochrome b5:oxygen oxidoreductase (C4-hydroxylating)

Comments: The enzyme, which belongs to the familiy of endoplasmic reticular cytochrome b5-dependent enzymes, is involved in the biosynthesis of sphingolipids in eukaryotes. Some enzymes are bifunctional and also catalyse EC 1.14.19.17, sphingolipid 4-desaturase [4].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Haak, D., Gable, K., Beeler, T. and Dunn, T. Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p. J. Biol. Chem. 272 (1997) 29704-29710. [PMID: 9368039]

2. Grilley, M.M., Stock, S.D., Dickson, R.C., Lester, R.L. and Takemoto, J.Y. Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae. J. Biol. Chem. 273 (1998) 11062-11068. [PMID: 9556590]

3. Sperling, P., Ternes, P., Moll, H., Franke, S., Zähringer, U. and Heinz, E. Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis thaliana. FEBS Lett. 494 (2001) 90-94. [PMID: 11297741]

4. Ternes, P., Franke, S., Zähringer, U., Sperling, P. and Heinz, E. Identification and characterization of a sphingolipid Δ4-desaturase family. J. Biol. Chem. 277 (2002) 25512-25518. [PMID: 11937514]

5. Mizutani, Y., Kihara, A. and Igarashi, Y. Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation. FEBS Lett. 563 (2004) 93-97. [PMID: 15063729]

[EC 1.14.18.5 created 2012 as EC 1.14.13.169, transferred 2015 to EC 1.14.18.5]

EC 1.14.18.6

Accepted name: 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase

Reaction: a phytoceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (2'R)-2'-hydroxyphytoceramide + 2 ferricytochrome b5 + H2O

Glossary: a phytoceramide = a (4R)-4-hydroxysphinganine ceramide = an N-acyl-4-hydroxysphinganine

Other name(s): FA2H (gene name); SCS7 (gene name)

Systematic name: (4R)-4-hydroxysphinganine ceramide,ferrocytochrome-b5:oxygen oxidoreductase (fatty acyl 2-hydroxylating)

Comments: The enzyme, characterized from yeast and mammals, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to (4R)-4-hydroxysphinganine during de novo ceramide synthesis. The enzymes from yeast and from mammals contain an N-terminal cytochrome b5 domain that acts as the direct electron donor to the desaturase active site. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.7, dihydroceramide fatty acyl 2-hydroxylase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Mitchell, A.G. and Martin, C.E. Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion protein, and its Arabidopsis thaliana homolog that lacks the cytochrome b5 domain both function in the α-hydroxylation of sphingolipid-associated very long chain fatty acids. J. Biol. Chem. 272 (1997) 28281-28288. [PMID: 9353282]

2. Dunn, T.M., Haak, D., Monaghan, E. and Beeler, T.J. Synthesis of monohydroxylated inositolphosphorylceramide (IPC-C) in Saccharomyces cerevisiae requires Scs7p, a protein with both a cytochrome b5-like domain and a hydroxylase/desaturase domain. Yeast 14 (1998) 311-321. [PMID: 9559540]

3. Alderson, N.L., Rembiesa, B.M., Walla, M.D., Bielawska, A., Bielawski, J. and Hama, H. The human FA2H gene encodes a fatty acid 2-hydroxylase. J. Biol. Chem. 279 (2004) 48562-48568. [PMID: 15337768]

4. Eckhardt, M., Yaghootfam, A., Fewou, S.N., Zoller, I. and Gieselmann, V. A mammalian fatty acid hydroxylase responsible for the formation of α-hydroxylated galactosylceramide in myelin. Biochem. J. 388 (2005) 245-254. [PMID: 15658937]

5. Guo, L., Zhang, X., Zhou, D., Okunade, A.L. and Su, X. Stereospecificity of fatty acid 2-hydroxylase and differential functions of 2-hydroxy fatty acid enantiomers. J. Lipid Res. 53 (2012) 1327-1335. [PMID: 22517924]

[EC 1.14.18.6 created 2015]

EC 1.14.18.7

Accepted name: dihydroceramide fatty acyl 2-hydroxylase

Reaction: a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (2'R)-2'-hydroxydihydroceramide + 2 ferricytochrome b5 + H2O

Glossary: a dihydroceramide = an N-acylsphinganine

Other name(s): FAH1 (gene name); FAH2 (gene name); plant sphingolipid fatty acid 2-hydroxylase

Systematic name: dihydroceramide,ferrocytochrome-b5:oxygen oxidoreductase (fatty acyl 2-hydroxylating)

Comments: The enzyme, characterized from plants, catalyses the hydroxylation of carbon 2 of long- or very-long-chain fatty acids attached to sphinganine during de novo ceramide synthesis. The enzyme requires an external cytochrome b5 as the electron donor. The newly introduced 2-hydroxyl group has R-configuration. cf. EC 1.14.18.6, 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Nagano, M., Ihara-Ohori, Y., Imai, H., Inada, N., Fujimoto, M., Tsutsumi, N., Uchimiya, H. and Kawai-Yamada, M. Functional association of cell death suppressor, Arabidopsis Bax inhibitor-1, with fatty acid 2-hydroxylation through cytochrome b5. Plant J. 58 (2009) 122-134. [PMID: 19054355]

2. Nagano, M., Takahara, K., Fujimoto, M., Tsutsumi, N., Uchimiya, H. and Kawai-Yamada, M. Arabidopsis sphingolipid fatty acid 2-hydroxylases (AtFAH1 and AtFAH2) are functionally differentiated in fatty acid 2-hydroxylation and stress responses. Plant Physiol. 159 (2012) 1138-1148. [PMID: 22635113]

3. Nagano, M., Uchimiya, H. and Kawai-Yamada, M. Plant sphingolipid fatty acid 2-hydroxylases have unique characters unlike their animal and fungus counterparts. Plant Signal Behav 7 (2012) 1388-1392. [PMID: 22918503]

[EC 1.14.18.7 created 2015]

EC 1.14.18.8

Accepted name: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase

Reaction: 7α-hydroxycholest-4-en-3-one + 2 ferrocytochrome b5 + 2 H+ + O2 = 7α,12α-dihydroxycholest-4-en-3-one + 2 ferricytochrome b5 + + H2O

For diagram of reaction click here.

Other name(s): 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; CYP12; sterol 12α-hydroxylase (ambiguous); HCO 12α-hydroxylase

Systematic name: 7α-hydroxycholest-4-en-3-one,ferrocytochrome-b5:oxygen oxidoreductase (12α-hydroxylating)

Comments: A P-450 heme-thiolate protein. Requires EC 1.6.2.4, NADPH—hemoprotein reductase and cytochrome b5 for maximal activity. This enzyme is important in bile acid biosynthesis, being responsible for the balance between the formation of cholic acid and chenodeoxycholic acid [2].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Ishida, H., Noshiro, M., Okuda, K. and Coon, M.J. Purification and characterization of 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase. J. Biol. Chem. 267 (1992) 21319-21323. [PMID: 1400444]

2. Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K.I. and Björkhem, I. Molecular cloning and expression of rabbit sterol 12α-hydroxylase. J. Biol. Chem. 271 (1996) 32269-32275. [PMID: 8943286]

3. Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137-174. [PMID: 12543708]

[EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8]

EC 1.14.18.9

Accepted name: methylsterol monooxygenase

Reaction: 4,4-dimethyl-5α-cholest-7-en-3β-ol + 6 ferrocytochrome b5 + 3 O2 + 6 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 6 ferricytochrome b5 + 4 H2O (overall reaction)
(1a) 4,4-dimethyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 4β-hydroxymethyl-4α-methyl-5α-cholest-7-en-3β-ol + 2 ferricytochrome b5 + H2O
(1b) 4β-hydroxymethyl-4α-methyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferricytochrome b5 + 2 H2O
(1c) 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferrocytochrome b5 + O2 + 2 H+ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 2 ferricytochrome b5 + H2O

For diagram of reaction click here

Other name(s): methylsterol hydroxylase; 4-methylsterol oxidase; 4,4-dimethyl-5α-cholest-7-en-3β-ol,hydrogen-donor:oxygen oxidoreductase (hydroxylating)

Systematic name: 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b5:oxygen oxidoreductase (hydroxylating)

Comments: Also acts on 4α-methyl-5α-cholest-7-en-3β-ol. The sterol can be based on cycloartenol as well as lanosterol.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Miller, W.L., Kalafer, M.E., Gaylor, J.L. and Delwicke, C.V. Investigation of the component reactions of oxidative sterol demethylation. Study of the aerobic and anaerobic processes. Biochemistry 6 (1967) 2673-2678. [PMID: 4383278]

2. Gaylor, J.L. and Mason, H.S. Investigation of the component reactions of oxidative sterol demethylation. Evidence against participation of cytochrome P-450. J. Biol. Chem. 243 (1968) 4966-4972. [PMID: 4234469]

3. Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624-10629. [PMID: 7430141]

4. Fukushima, H., Grinstead, G.F. and Gaylor, J.L. Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b5-dependence of 4-methyl sterol oxidase. J. Biol. Chem. 256 (1981) 4822-4826. [PMID: 7228857]

5. Kawata, S., Trzaskos, J.M. and Gaylor, J.L. Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b5. J. Biol. Chem. 261 (1986) 3790-3799. [PMID: 3949790]

6. Pascal, S., Taton, M. and Rahier, A. Plant sterol biosynthesis. Identification and characterization of two distinct microsomal oxidative enzymatic systems involved in sterol C4-demethylation. J. Biol. Chem. 268 (1993) 11639-11654. [PMID: 8505296]

7. Rahier, A., Smith, M. and Taton, M. The role of cytochrome b5 in 4α-methyl-oxidation and C5(6) desaturation of plant sterol precursors. Biochem. Biophys. Res. Commun. 236 (1997) 434-437. [PMID: 9240456]

[EC 1.14.18.9 created 1972 as EC 1.14.99.16, transferred 2002 to EC 1.14.13.72, transferred 2017 to EC 1.14.18.9]


Continued with EC 1.14.19
Return to EC 1 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page