Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Kristian Axelsen, Richard Cammack, Ron Caspi, Masaaki Kotera, Andrew McDonald, Gerry Moss, Dietmar Schomburg, Ida Schomburg and Keith Tipton. Comments and suggestions on these draft entries should be sent to Dr Andrew McDonald (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland). The date on which an enzyme will be made official is appended after the EC number. To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


Contents

*EC 1.1.1.262 4-hydroxythreonine-4-phosphate dehydrogenase (17 June 2018)
EC 1.1.99.42 4-pyridoxic acid dehydrogenase (17 June 2018)
EC 1.2.1.100 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase (17 June 2018)
EC 1.3.1.114 3-dehydro-bile acid Δ4,6-reductase (17 June 2018)
EC 1.3.1.115 3-oxocholoyl-CoA 4-desaturase (17 June 2018)
EC 1.3.1.116 7β-hydroxy-3-oxochol-24-oyl-CoA 4-desaturase (17 June 2018)
EC 1.3.1.117 hydroxycinnamoyl-CoA reductase (17 June 2018)
EC 1.3.99.39 carotenoid φ-ring synthase (17 June 2018)
EC 1.3.99.40 carotenoid χ-ring synthase (17 June 2018)
EC 1.14.11.14 transferred now EC 1.14.20.13 (17 June 2018)
EC 1.14.12.4 transferred now EC 1.14.13.242 (17 June 2018)
EC 1.14.12.5 transferred now EC 1.14.13.241 (17 June 2018)
EC 1.14.13.21 transferred now EC 1.14.14.82 (17 June 2018)
*EC 1.14.13.32 albendazole monooxygenase (flavin-containing) (17 June 2018)
EC 1.14.13.74 transferred now EC 1.14.14.85 (17 June 2018)
EC 1.14.13.78 transferred now EC 1.14.14.86 (17 June 2018)
EC 1.14.13.88 transferred now EC 1.14.14.81 (17 June 2018)
EC 1.14.13.136 transferred now EC 1.14.14.87 (17 June 2018)
EC 1.14.13.141 transferred now EC 1.14.15.29 (17 June 2018)
EC 1.14.13.143 transferred now EC 1.14.14.76 (17 June 2018)
EC 1.14.13.151 transferred now EC 1.14.14.84 (17 June 2018)
EC 1.14.13.152 transferred now EC 1.14.14.83 (17 June 2018)
EC 1.14.13.194 transferred now EC 1.14.14.78 (17 June 2018)
EC 1.14.13.199 transferred now EC 1.14.14.79 (17 June 2018)
EC 1.14.13.205 transferred now EC 1.14.14.80 (17 June 2018)
EC 1.14.13.221 transferred now EC 1.14.15.28 (17 June 2018)
EC 1.14.13.240 2-polyprenylphenol 6-hydroxylase (17 June 2018)
EC 1.14.13.241 5-pyridoxate monooxygenase (17 June 2018)
EC 1.14.13.242 3-hydroxy-2-methylpyridine-5-carboxylate monooxygenase (17 June 2018)
*EC 1.14.14.56 1,8-cineole 2-exo-monooxygenase (17 June 2018)
EC 1.14.14.73 albendazole monooxygenase (sulfoxide-forming) (17 June 2018)
EC 1.14.14.74 albendazole monooxygenase (hydroxylating) (17 June 2018)
EC 1.14.14.75 fenbendazole monooxygenase (4'-hydroxylating) (17 June 2018)
EC 1.14.14.76 ent-isokaurene C2/C3-hydroxylase (17 June 2018)
EC 1.14.14.77 phenylacetonitrile α-monooxygenase (17 June 2018)
EC 1.14.14.78 phylloquinone ω-hydroxylase (17 June 2018)
EC 1.14.14.79 docosahexaenoic acid ω-hydroxylase (17 June 2018)
EC 1.14.14.80 long-chain fatty acid ω-monooxygenase (17 June 2018)
EC 1.14.14.81 flavanoid 3',5'-hydroxylase (17 June 2018)
EC 1.14.14.82 flavonoid 3'-monooxygenase (17 June 2018)
EC 1.14.14.83 geraniol 8-hydroxylase (17 June 2018)
EC 1.14.14.84 linalool 8-monooxygenase (17 June 2018)
EC 1.14.14.85 7-deoxyloganin 7-hydroxylase (17 June 2018)
EC 1.14.14.86 ent-kaurene monooxygenase (17 June 2018)
EC 1.14.14.87 2-hydroxyisoflavanone synthase (17 June 2018)
EC 1.14.15.27 β-dihydromenaquinone-9 ω-hydroxylase (17 June 2018)
EC 1.14.15.28 cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming] (17 June 2018)
EC 1.14.15.29 cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming] (17 June 2018)
EC 1.14.15.30 3-ketosteroid 9α-monooxygenase (17 June 2018)
EC 1.14.19.61 dihydrorhizobitoxine desaturase (17 June 2018)
EC 1.14.20.9 L-tyrosine isonitrile desaturase (17 June 2018)
EC 1.14.20.10 L-tyrosine isonitrile desaturase/decarboxylase (17 June 2018)
EC 1.14.20.11 3-[(Z)-2-isocyanoethenyl]-1H-indole synthase (17 June 2018)
EC 1.14.20.12 3-[(E)-2-isocyanoethenyl]-1H-indole synthase (17 June 2018)
EC 1.14.20.13 6β-hydroxyhyoscyamine epoxidase (17 June 2018)
EC 1.14.99.60 3-demethoxyubiquinol 3-hydroxylase (17 June 2018)
*EC 1.18.6.1 nitrogenase (17 June 2018)
EC 1.18.6.2 vanadium-dependent nitrogenase (17 June 2018)
*EC 2.3.1.74 chalcone synthase (17 June 2018)
*EC 2.3.1.97 glycylpeptide N-tetradecanoyltransferase (17 June 2018)
EC 2.3.1.269 apolipoprotein N-acyltransferase (17 June 2018)
EC 2.3.1.270 lyso-ornithine lipid O-acyltransferase (17 June 2018)
EC 2.3.1.271 L-glutamate-5-semialdehyde N-acetyltransferase (17 June 2018)
EC 2.3.1.272 2-acetylphloroglucinol acetyltransferase (17 June 2018)
EC 2.4.1.95 deleted (17 June 2018)
*EC 2.4.1.102 β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,6-N-acetylglucosaminyltransferase (17 June 2018)
*EC 2.4.1.146 β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,3-N-acetylglucosaminyltransferase (17 June 2018)
*EC 2.4.1.155 α-1,6-mannosyl-glycoprotein 6-β-N-acetylglucosaminyltransferase (17 June 2018)
*EC 2.4.1.226 N-acetylgalactosaminyl-proteoglycan 3-β-glucuronosyltransferase (17 June 2018)
EC 2.4.1.356 glucosyl-dolichyl phosphate glucuronosyltransferase (17 June 2018)
EC 2.4.1.357 phlorizin synthase (17 June 2018)
EC 2.5.1.144 S-sulfo-L-cysteine synthase (O-acetyl-L-serine-dependent) (17 June 2018)
EC 2.5.1.145 phosphatidylglycerol—prolipoprotein diacylglyceryl transferase (17 June 2018)
EC 2.5.1.146 3-geranyl-3-[(Z)-2-isocyanoethenyl]indole synthase (17 June 2018)
*EC 2.6.1.92 UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine transaminase (17 June 2018)
EC 2.7.7.100 SAMP-activating enzyme (17 June 2018)
EC 2.8.5 Thiosulfotransferases (17 June 2018)
EC 2.8.5.1 S-sulfo-L-cysteine synthase (3-phospho-L-serine-dependent) (17 June 2018)
EC 3.1.6.20 S-sulfosulfanyl-L-cysteine sulfohydrolase (17 June 2018)
*EC 3.2.1.170 mannosylglycerate hydrolase (17 June 2018)
*EC 3.3.1.2 S-adenosyl-L-methionine hydrolase (L-homoserine-forming) (17 June 2018)
EC 3.13.1.8 S-adenosyl-L-methionine hydrolase (adenosine-forming) (17 June 2018)
EC 4.1.1.110 bisphosphomevalonate decarboxylase (17 June 2018)
EC 4.1.1.111 siroheme decarboxylase (17 June 2018)
EC 4.4.1.37 pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase (17 June 2018)
EC 6.2.1.55 E1 SAMP-activating enzyme (17 June 2018)

*EC 1.1.1.262

Accepted name: 4-hydroxythreonine-4-phosphate dehydrogenase

Reaction: 4-phosphooxy-L-threonine + NAD+ = 3-amino-2-oxopropyl phosphate + CO2 + NADH + H+

For diagram of reaction click here.

Other name(s): NAD+-dependent threonine 4-phosphate dehydrogenase; L-threonine 4-phosphate dehydrogenase; 4-(phosphohydroxy)-L-threonine dehydrogenase; PdxA; 4-(phosphonooxy)-L-threonine:NAD+ oxidoreductase; 4-phosphooxy-L-threonine:NAD+ oxidoreductase

Systematic name: 4-phosphooxy-L-threonine:NAD+ 3-oxidoreductase (decarboxylating)

Comments: The enzyme is part of the biosynthesis pathway of the coenzyme pyridoxal 5'-phosphate found in anaerobic bacteria.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 230310-36-8

References:

1. Cane, D.E., Hsiung, Y., Cornish, J.A., Robinson, J.K and Spenser, I.D. Biosynthesis of vitamine B6: The oxidation of L-threonine 4-phosphate by PdxA. J. Am. Chem. Soc. 120 (1998) 1936-1937.

2. Laber, B., Maurer, W., Scharf, S., Stepusin, K. and Schmidt, F.S. Vitamin B6 biosynthesis: formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein. FEBS Lett. 449 (1999) 45-48. [PMID: 10225425]

3. Sivaraman, J., Li, Y., Banks, J., Cane, D.E., Matte, A. and Cygler, M. Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway. J. Biol. Chem. 278 (2003) 43682-43690. [PMID: 12896974]

4. Banks, J. and Cane, D.E. Biosynthesis of vitamin B6: direct identification of the product of the PdxA-catalyzed oxidation of 4-hydroxy-l-threonine-4-phosphate using electrospray ionization mass spectrometry. Bioorg. Med. Chem. Lett. 14 (2004) 1633-1636. [PMID: 15026039]

[EC 1.1.1.262 created 2000, modified 2006, modified 2018]

EC 1.1.99.42

Accepted name: 4-pyridoxic acid dehydrogenase

Reaction: 4-pyridoxate + acceptor = 5-formyl-3-hydroxy-2-methylpyridine-4-carboxylate + reduced acceptor

For diagram of reaction click here.

Glossary: 4-pyridoxate = 3-hydroxy-5-(hydroxymethyl)-2-methylpyridine-4-carboxylate
dichloroindophenol = DCPIP = 2,6-dichloro-4-[(4-hydroxyphenyl)imino]cyclohexa-2,5-dien-1-one

Other name(s): mlr6792 (locus name)

Systematic name: 4-pyridoxate:acceptor 5-oxidoreductase

Comments: The enzyme, characterized from the bacteria Pseudomonas sp. MA-1 and Mesorhizobium loti, participates in the degradation of pyridoxine (vitamin B6). It is membrane bound and contains FAD. The enzyme has been assayed in vitro in the presence of the artificial electron acceptor dichloroindophenol (DCPIP).

References:

1. Yagi, T., Kishore, G.M. and Snell, E.E. The bacterial oxidation of vitamin B6. 4-Pyridoxic acid dehydrogenase: a membrane-bound enzyme from Pseudomonas MA-1. J. Biol. Chem 258 (1983) 9419-9425. [PMID: 6348042]

2. Ge, F., Yokochi, N., Yoshikane, Y., Ohnishi, K. and Yagi, T. Gene identification and characterization of the pyridoxine degradative enzyme 4-pyridoxic acid dehydrogenase from the nitrogen-fixing symbiotic bacterium Mesorhizobium loti MAFF303099. J. Biochem. 143 (2008) 603-609. [PMID: 18216065]

[EC 1.1.99.42 created 2018]

EC 1.2.1.100

Accepted name: 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase

Reaction: 5-formyl-3-hydroxy-2-methylpyridine-4-carboxylate + NAD+ + H2O = 3-hydroxy-2-methylpyridine-4,5-dicarboxylate + NADH + H+

Other name(s): mlr6793 (locus name)

Systematic name: 5-formyl-3-hydroxy-2-methylpyridine-4-carboxylate:NAD+ 5-oxidoreductase

Comments: The enzyme, characterized from the bacteria Pseudomonas sp. MA-1 and Mesorhizobium loti, participates in the degradation of pyridoxine (vitamin B6).

References:

1. Lee, Y.C., Nelson, M.J. and Snell, E.E. Enzymes of vitamin B6 degradation. Purification and properties of isopyridoxal dehydrogenase and 5-formyl-3-hydroxy-2-methylpyridine-4-carboxylic-acid dehydrogenase. J. Biol. Chem 261 (1986) 15106-15111. [PMID: 3533936]

2. Yokochi, N., Yoshikane, Y., Matsumoto, S., Fujisawa, M., Ohnishi, K. and Yagi, T. Gene identification and characterization of 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase, an NAD+-dependent dismutase. J. Biochem. 145 (2009) 493-503. [PMID: 19218190]

3. Mugo, A.N., Kobayashi, J., Mikami, B., Yoshikane, Y., Yagi, T. and Ohnishi, K. Crystal structure of 5-formyl-3-hydroxy-2-methylpyridine 4-carboxylic acid 5-dehydrogenase, an NAD(+)-dependent dismutase from Mesorhizobium loti. Biochem. Biophys. Res. Commun. 456 (2015) 35-40. [PMID: 25446130]

[EC 1.2.1.100 created 2018]

EC 1.3.1.114

Accepted name: 3-dehydro-bile acid Δ4,6-reductase

Reaction: (1) 3-oxocholan-24-oyl-CoA + NAD+ = 3-oxochol-4-en-24-oyl-CoA + NADH + H+
(2) 3-oxochol-4-en-24-oyl-CoA + NAD+ = 3-oxochol-4,6-dien-24-oyl-CoA + NADH + H+
(3) 12α-hydroxy-3-oxocholan-24-oyl-CoA + NAD+ = 12α-hydroxy-3-oxochol-4-en-24-oyl-CoA + NADH + H+
(4) 12α-hydroxy-3-oxochol-4-en-24-oyl-CoA + NAD+ = 12α-hydroxy-3-oxochol-4,6-dien-24-oyl-CoA + NADH + H+

Other name(s): baiN (gene name)

Systematic name: 3-oxocholan-24-oyl-CoA Δ4,6-oxidoreductase

Comments: Contains flavin. The enzyme, characterized from the bacterium Clostridium scindens, participates in the bile acid 7α-dehydroxylation pathway. The enzyme catalyses two subsequent reductions of the double bonds within the bile acid A/B rings, following 7α-dehydration.

References:

1. Harris, S.C., Devendran, S., Alves, J.MP., Mythen, S.M., Hylemon, P.B. and Ridlon, J.M. Identification of a gene encoding a flavoprotein involved in bile acid metabolism by the human gut bacterium Clostridium scindens ATCC 35704. Biochim. Biophys. Acta 1863 (2018) 276-283. [PMID: 29217478]

[EC 1.3.1.114 created 2018]

EC 1.3.1.115

Accepted name: 3-oxocholoyl-CoA 4-desaturase

Reaction: (1) 7α,12α-dihydroxy-3-oxochol-24-oyl-CoA + NAD+ = 7α,12α-dihydroxy-3-oxochol-4-en-24-oyl-CoA + NADH + H+
(2) 7α-hydroxy-3-oxochol-24-oyl-CoA + NAD+ = 7α-hydroxy-3-oxochol-4-en-24-oyl-CoA + NADH + H+

Glossary: 7α,12α-dihydroxy-3-oxochol-24-oyl-CoA = 3-oxocholoyl-CoA
7α-hydroxy-3-oxochol-24-oyl-CoA = 3-oxochenodeoxycholoyl-CoA

Other name(s): baiCD (gene name); 3-oxo-choloyl-CoA dehydrogenase

Systematic name: 3-oxocholoyl-CoA Δ4-oxidoreductase

Comments: Contains flavin. The enzyme, characterized from the bacterium Clostridium scindens, participates in the bile acid 7α-dehydroxylation pathway. The enzyme catalyses the stereo-specific oxidation of its substrates and has no activity with the 7β anomers. cf. EC 1.3.1.116, 7β-hydroxy-3-oxochol-24-oyl-CoA 4-desaturase.

References:

1. Kang, D.J., Ridlon, J.M., Moore, D.R., 2nd, Barnes, S. and Hylemon, P.B. Clostridium scindens baiCD and baiH genes encode stereo-specific 7α/7β-hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductases. Biochim. Biophys. Acta 1781 (2008) 16-25. [PMID: 18047844]

[EC 1.3.1.115 created 2018]

EC 1.3.1.116

Accepted name: 7β-hydroxy-3-oxochol-24-oyl-CoA 4-desaturase

Reaction: 7β-hydroxy-3-oxochol-24-oyl-CoA + NAD+ = 7β-hydroxy-3-oxochol-4-en-24-oyl-CoA + NADH + H+

Other name(s): baiH (gene name)

Systematic name: 7β-hydroxy-3-oxochol-24-oyl-CoA Δ4-oxidoreductase

Comments: Contains FAD and FMN. The enzyme, characterized from the bacterium Clostridium scindens, participates in the bile acid 7α-dehydroxylation pathway. The enzyme catalyses the stereo-specific oxidation of its substrate and has no activity with the 7α anomer. cf. EC 1.3.1.115, 3-oxocholoyl-CoA 4-desaturase.

References:

1. Baron, S.F. and Hylemon, P.B. Expression of the bile acid-inducible NADH:flavin oxidoreductase gene of Eubacterium sp. VPI 12708 in Escherichia coli. Biochim. Biophys. Acta 1249 (1995) 145-154. [PMID: 7599167]

2. Franklund, C.V., Baron, S.F. and Hylemon, P.B. Characterization of the baiH gene encoding a bile acid-inducible NADH:flavin oxidoreductase from Eubacterium sp. strain VPI 12708. J. Bacteriol. 175 (1993) 3002-3012. [PMID: 8491719]

3. Kang, D.J., Ridlon, J.M., Moore, D.R., 2nd, Barnes, S. and Hylemon, P.B. Clostridium scindens baiCD and baiH genes encode stereo-specific 7α/7β-hydroxy-3-oxo-Δ4-cholenoic acid oxidoreductases. Biochim. Biophys. Acta 1781 (2008) 16-25. [PMID: 18047844]

[EC 1.3.1.116 created 2018]

EC 1.3.1.117

Accepted name: hydroxycinnamoyl-CoA reductase

Reaction: (1) dihydro-4-coumaroyl-CoA + NADP+ = trans-4-coumaroyl-CoA + NADPH + H+
(2) dihydroferuloyl-CoA + NADP+ = trans-feruloyl-CoA + NADPH + H+

For diagram of reaction click here.

Glossary: trans-4-coumaroyl-CoA = (E)-3-(4-hydroxyphenyl)prop-2-enoyl-CoA
trans-feruloyl-CoA = (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl-CoA
dihydro-4-coumaroyl-CoA = 3-(4-hydroxyphenyl)propanoyl-CoA
dihydroferuloyl-CoA = 3-(4-hydroxy-3-methoxyphenyl)propanoyl-CoA

Other name(s): MdHCDBR; hydroxycinnamoyl-CoA double bond reductase

Systematic name: dihydro-4-coumaroyl-CoA:NADP+ 2,3-oxidoreductase

Comments: Isolated from Malus X domestica (apple). Involved in dihydrochalcone biosynthesis.

References:

1. Ibdah, M., Berim, A., Martens, S., Valderrama, A.L.H., Palmieri, L., Lewinsohn, E. and Gang, D.R. Identification and cloning of an NADPH-dependant hydroxycinnamoyl-CoA double bond reductase involved in dihydrochalcone formation in Malus X domestica Borkh. Phytochemistry 107 (2014) 24-31. [PMID: 25152451]

[EC 1.3.1.117 created 2018]

EC 1.3.99.39

Accepted name: carotenoid φ-ring synthase

Reaction: carotenoid β-end group + 2 acceptor = carotenoid φ-end group + 2 reduced acceptor

For diagram of reaction click here.

Glossary: chlorobactene = φ,ψ-carotene
β-isorenieratene = φ,β-carotene
isorenieratene = φ,φ-carotene

Other name(s): crtU (gene name)

Systematic name: carotenoid β-ring:acceptor oxidoreductase/methyltranferase (φ-ring forming)

Comments: The enzyme, found in green sulfur bacteria, some cyanobacteria and some actinobacteria, introduces additional double bonds to the carotenoid β-end group, leading to aromatization of the ionone ring. As a result, one of the methyl groups at C-1 is transferred to position C-2. It is involved in the biosynthesis of carotenoids with φ-type aromatic end groups such as chlorobactene, β-isorenieratene, and isorenieratene.

References:

1. Moshier, S.E. and Chapman, D.J. Biosynthetic studies on aromatic carotenoids. Biosynthesis of chlorobactene. Biochem. J. 136 (1973) 395-404. [PMID: 4774401]

2. Krugel, H., Krubasik, P., Weber, K., Saluz, H.P. and Sandmann, G. Functional analysis of genes from Streptomyces griseus involved in the synthesis of isorenieratene, a carotenoid with aromatic end groups, revealed a novel type of carotenoid desaturase. Biochim. Biophys. Acta 1439 (1999) 57-64. [PMID: 10395965]

3. Frigaard, N.U., Maresca, J.A., Yunker, C.E., Jones, A.D. and Bryant, D.A. Genetic manipulation of carotenoid biosynthesis in the green sulfur bacterium Chlorobium tepidum. J. Bacteriol. 186 (2004) 5210-5220. [PMID: 15292122]

[EC 1.3.99.39 created 2018]

EC 1.3.99.40

Accepted name: carotenoid χ-ring synthase

Reaction: carotenoid β-end group + 2 acceptor = carotenoid χ-end group + 2 reduced acceptor

For diagram of reaction click here.

Glossary: okenone = 1'-methoxy-1',2'-dihydro-χ,ψ-caroten-4'-one
renierapurpurin = χ,χ-carotene
synechoxanthin = χ,χ-caroten-18,18'-dioate

Other name(s): crtU (gene name); cruE (gene name)

Systematic name: carotenoid β-ring:acceptor oxidoreductase/methyltranferase (χ-ring forming)

Comments: The enzyme, found in purple sulfur bacteria (Chromatiaceae) and some cyanobacteria, is involved in the biosynthesis of carotenoids that contain χ-type end groups, such as okenone, renierapurpurin, and synechoxanthin.

References:

1. Graham, J.E. and Bryant, D.A. The Biosynthetic pathway for synechoxanthin, an aromatic carotenoid synthesized by the euryhaline, unicellular cyanobacterium Synechococcus sp. strain PCC 7002. J. Bacteriol. 190 (2008) 7966-7974. [PMID: 18849428]

2. Vogl, K. and Bryant, D.A. Biosynthesis of the biomarker okenone: χ-ring formation. Geobiology 10 (2012) 205-215. [PMID: 22070388]

[EC 1.3.99.40 created 2018]

[EC 1.14.11.14 Transferred entry: 6β-hydroxyhyoscyamine epoxidase. Now EC 1.14.20.13, 6β-hydroxyhyoscyamine epoxidase (EC 1.14.11.14 created 1992, deleted 2018)]

[EC 1.14.12.4 Transferred entry: 3-hydroxy-2-methylpyridinecarboxylate dioxygenase. Now EC 1.14.13.242, 3-hydroxy-2-methylpyridinecarboxylate monooxygenase (EC 1.14.12.4 created 1972, deleted 2018)]

[EC 1.14.12.5 Transferred entry: 5-pyridoxate dioxygenase. Now EC 1.14.13.241, 5-pyridoxate monooxygenase (EC 1.14.12.5 created 1972, deleted 2018)]

[EC 1.14.13.21 Transferred entry: flavonoid 3'-monooxygenase. Now EC 1.14.14.82, flavonoid 3'-monooxygenase. (EC 1.14.13.21 created 1983, deleted 2018)]

*EC 1.14.13.32

Accepted name: albendazole monooxygenase

Reaction: albendazole + NADPH + H+ + O2 = albendazole S-oxide + NADP+ + H2O

Glossary: albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate

Other name(s): albendazole oxidase (misleading); albendazole sulfoxidase (ambiguous); FMO3 (gene name); albendazole monooxygenase (flavin-containing)

Systematic name: albendazole,NADPH:oxygen oxidoreductase (sulfoxide-forming)

Comments: A microsomal flavin-containing monooxygenase. A similar conversion is also carried out by some microsomal cytochrome P-450 enzymes [EC 1.14.14.73, albendazole monooxygenase (sulfoxide-forming)]. It is estimated that cytochrome P-450s are responsible for 70% of the activity.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 101299-59-6

References:

1. Fargetton, X., Galtier, P. and Delatour, P. Sulfoxidation of albendazole by a cytochrome P450-independent monooxygenase from rat liver microsomes. Vet. Res. Commun. 10 (1986) 317-324. [PMID: 3739217]

2. Moroni, P., Buronfosse, T., Longin-Sauvageon, C., Delatour, P. and Benoit, E. Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes. Drug Metab. Dispos. 23 (1995) 160-165. [PMID: 7736906]

3. Rawden, H.C., Kokwaro, G.O., Ward, S.A. and Edwards, G. Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes. Br. J. Clin. Pharmacol. 49 (2000) 313-322. [PMID: 10759686]

[EC 1.14.13.32 created 1989, modified 2018]

[EC 1.14.13.74 Transferred entry: 7-deoxyloganin 7-hydroxylase. Now EC 1.14.14.85, 7-deoxyloganin 7-hydroxylase (EC 1.14.13.74 created 2002, deleted 2018)]

[EC 1.14.13.78 Transferred entry: ent-kaurene oxidase. Now EC 1.14.14.86, ent-kaurene monooxygenase (EC 1.14.13.78 created 2002, deleted 2018)]

[EC 1.14.13.88 Transferred entry: flavanoid 3',5'-hydroxylase. Now EC 1.14.14.81, flavanoid 3',5'-hydroxylase (EC 1.14.13.88 created 2004, deleted 2018)]

[EC 1.14.13.136 Transferred entry: 2-hydroxyisoflavanone synthase. Now EC 1.14.14.87, 2-hydroxyisoflavanone synthase (EC 1.14.13.136 created 2011, modified 2013, deleted 2018)]

[EC 1.14.13.141 Transferred entry: cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming] (EC 1.14.13.141 created 2012, modified 2016, deleted 2018)]

[EC 1.14.13.143 Transferred entry: ent-isokaurene C2-hydroxylase. Now EC 1.14.14.76 ent-isokaurene C2/C3-hydroxylase (EC 1.14.13.143 created 2012, deleted 2018)]

[EC 1.14.13.151 Transferred entry: linalool 8-monooxygenase. Now EC 1.14.14.84, linalool 8-monooxygenase (EC 1.14.13.151 created 1989 as EC 1.14.99.28, transferred 2012 to EC 1.14.13.151, deleted 2018)]

[EC 1.14.13.152 Transferred entry: geraniol 8-hydroxylase. Now EC 1.14.14.83, geraniol 8-hydroxylase (EC 1.14.13.152 created 2012, deleted 2018)]

[EC 1.14.13.194 Transferred entry: phylloquinone ω-hydroxylase. Now EC 1.14.14.78, phylloquinone ω-hydroxylase (EC 1.14.13.194 created 2014, deleted 2018)]

[EC 1.14.13.199 Transferred entry: docosahexaenoic acid ω-hydroxylase. Now EC 1.14.14.79, docosahexaenoic acid ω-hydroxylase (EC 1.14.13.199 created 2014, deleted 2018)]

[EC 1.14.13.205 Transferred entry: long-chain fatty acid ω-monooxygenase. Now EC 1.14.14.80, long-chain fatty acid ω-monooxygenase (EC 1.14.13.205 created 2015, deleted 2018)]

[EC 1.14.13.221 Transferred entry: cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]. Now EC 1.14.15.28, cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming] (EC 1.14.13.221 created 2016, deleted 2018)]

EC 1.14.13.240

Accepted name: 2-polyprenylphenol 6-hydroxylase

Reaction: 2-(all-trans-polyprenyl)phenol + NADPH + H+ + O2 = 3-(all-trans-polyprenyl)benzene-1,2-diol + NADP+ + H2O

Other name(s): ubiI (gene name); ubiM (gene name)

Systematic name: 2-(all-trans-polyprenyl)phenol,NADPH:oxygen oxidoreductase (6-hydroxylating)

Comments: Contains FAD. The enzyme from the bacterium Escherichia coli (UbiI) catalyses the first hydroxylation during the aerobic biosynthesis of ubiquinone. The enzyme from the bacterium Neisseria meningitidis (UbiM) can also catalyse the two additional hydroxylations that occur in the pathway (cf. EC 1.14.99.60, 3-demethoxyubiquinol 3-hydroxylase).

References:

1. Young, I.G., McCann, L.M., Stroobant, P. and Gibson, F. Characterization and genetic analysis of mutant strains of Escherichia coli K-12 accumulating the biquinone precursors 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone. J. Bacteriol. 105 (1971) 769-778. [PMID: 4323297]

2. Kwon, O., Kotsakis, A. and Meganathan, R. Ubiquinone (coenzyme Q) biosynthesis in Escherichia coli: identification of the ubiF gene. FEMS Microbiol. Lett. 186 (2000) 157-161. [PMID: 10802164]

[EC 1.14.13.240 created 2018]

EC 1.14.13.241

Accepted name: 5-pyridoxate monooxygenase

Reaction: 3-hydroxy-4-hydroxymethyl-2-methylpyridine-5-carboxylate + NADPH + H+ + O2 = 2-(acetamidomethylene)-3-(hydroxymethyl)succinate + NADP+

Glossary: 3-hydroxy-4-hydroxymethyl-2-methylpyridine-5-carboxylate = 5-pyridoxate

Other name(s): 5-pyridoxate,NADPH:oxygen oxidoreductase (decyclizing); 5-pyridoxate oxidase (misleading); 5-pyridoxate dioxygenase (incorrect)

Systematic name: 5-pyridoxate,NADPH:oxygen oxidoreductase (ring-opening)

Comments: Contains FAD. The enzyme, characterized from the bacterium Arthrobacter sp. Cr-7, participates in the degradation of pyridoxine (vitamin B6). Although the enzyme was initially thought to be a dioxygenase, oxygen-tracer experiments have suggested that it is a monooxygenase, incorporating only one oxygen atom from molecular oxygen into the product. The second oxygen atom originates from a water molecule, which is regenerated during the reaction and thus does not show up in the reaction equation.

References:

1. Sparrow, L.G., Ho, P.P.K., Sundaram, T.K., Zach, D., Nyns, E.J. and Snell, E.E. The bacterial oxidation of vitamin B6. VII. Purification, properties, and mechanism of action of an oxygenase which cleaves the 3-hydroxypyridine ring. J. Biol. Chem. 244 (1969) 2590-2600. [PMID: 4306031]

2. Nelson, M.J. and Snell, E.E. Enzymes of vitamin B6 degradation. Purification and properties of 5-pyridoxic-acid oxygenase from Arthrobacter sp. J. Biol. Chem 261 (1986) 15115-15120. [PMID: 3771566]

3. Chaiyen, P. Flavoenzymes catalyzing oxidative aromatic ring-cleavage reactions. Arch. Biochem. Biophys. 493 (2010) 62-70. [PMID: 19728986]

[EC 1.14.13.241 created 2018 (EC 1.14.12.5 created 1972, incorporated 2018)]

EC 1.14.13.242

Accepted name: 3-hydroxy-2-methylpyridine-5-carboxylate monooxygenase

Reaction: 3-hydroxy-2-methylpyridine-5-carboxylate + NAD(P)H + H+ + O2 = 2-(acetamidomethylidene)succinate + NAD(P)+

For diagram of reaction click here.

Other name(s): MHPCO; 3-hydroxy-2-methylpyridine-5-carboxylate,NAD(P)H:oxygen oxidoreductase (decyclizing); methylhydroxypyridinecarboxylate oxidase (misleading); 2-methyl-3-hydroxypyridine 5-carboxylic acid dioxygenase (incorrect); methylhydroxypyridine carboxylate dioxygenase (incorrect); 3-hydroxy-3-methylpyridinecarboxylate dioxygenase [incorrect]; 3-hydroxy-2-methylpyridinecarboxylate dioxygenase (incorrect)

Systematic name: 3-hydroxy-2-methylpyridine-5-carboxylate,NAD(P)H:oxygen oxidoreductase (ring-opening)

Comments: Contains FAD. The enzyme, characterized from the bacteria Pseudomonas sp. MA-1 and Mesorhizobium loti, participates in the degradation of pyridoxine (vitamin B6). Although the enzyme was initially thought to be a dioxygenase, oxygen-tracer experiments have shown that it is a monooxygenase, incorporating only one oxygen atom from molecular oxygen. The second oxygen atom that is incorporated into the product originates from a water molecule, which is regenerated during the reaction and thus does not show up in the reaction equation.

References:

1. Sparrow, L.G., Ho, P.P.K., Sundaram, T.K., Zach, D., Nyns, E.J. and Snell, E.E. The bacterial oxidation of vitamin B6. VII. Purification, properties, and mechanism of action of an oxygenase which cleaves the 3-hydroxypyridine ring. J. Biol. Chem. 244 (1969) 2590-2600. [PMID: 4306031]

2. Chaiyen, P., Ballou, D.P. and Massey, V. Gene cloning, sequence analysis, and expression of 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase. Proc. Natl Acad. Sci. USA 94 (1997) 7233-7238. [PMID: 9207074]

3. Oonanant, W., Sucharitakul, J., Yuvaniyama, J. and Chaiyen, P. Crystallization and preliminary X-ray crystallographic analysis of 2-methyl-3-hydroxypyridine-5-carboxylic acid (MHPC) oxygenase from Pseudomonas sp. MA-1. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 312-314. [PMID: 16511028]

4. Yuan, B., Yokochi, N., Yoshikane, Y., Ohnishi, K. and Yagi, T. Molecular cloning, identification and characterization of 2-methyl-3-hydroxypyridine-5-carboxylic-acid-dioxygenase-coding gene from the nitrogen-fixing symbiotic bacterium Mesorhizobium loti. J. Biosci. Bioeng. 102 (2006) 504-510. [PMID: 17270714]

5. McCulloch, K.M., Mukherjee, T., Begley, T.P. and Ealick, S.E. Structure of the PLP degradative enzyme 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase from Mesorhizobium loti MAFF303099 and its mechanistic implications. Biochemistry 48 (2009) 4139-4149. [PMID: 19317437]

6. Tian, B., Tu, Y., Strid, A. and Eriksson, L.A. Hydroxylation and ring-opening mechanism of an unusual flavoprotein monooxygenase, 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase: a theoretical study. Chemistry 16 (2010) 2557-2566. [PMID: 20066695]

7. Tian, B., Strid, A. and Eriksson, L.A. Catalytic roles of active-site residues in 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase: an ONIOM/DFT study. J. Phys. Chem. B 115 (2011) 1918-1926. [PMID: 21291225]

[EC 1.14.13.242 created 2018 (EC 1.14.12.4 created 1972, incorporated 2018)]

*EC 1.14.14.56

Accepted name: 1,8-cineole 2-exo-monooxygenase

Reaction: 1,8-cineole + [reduced NADPH—hemoprotein reductase] + O2 = 2-exo-hydroxy-1,8-cineole + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: 1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
2-exo-hydroxy-1,8-cineole = (1R,4S,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol

Other name(s): CYP3A4

Systematic name: 1,8-cineole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-exo-hydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein. The mammalian enzyme, expressed in liver microsomes, performs a variety of oxidation reactions of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. cf. EC 1.14.14.55, quinine 3-monooxygenase, EC 1.14.14.57, taurochenodeoxycholate 6-hydroxylase and EC 1.14.14.73, albendazole monooxygenase (sulfoxide-forming).

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

References:

1. Miyazawa, M., Shindo, M. and Shimada, T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from Eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab. Dispos. 29 (2001) 200-205. [PMID: 11159812]

2. Miyazawa, M. and Shindo, M. Biotransformation of 1,8-cineole by human liver microsomes. Nat. Prod. Lett. 15 (2001) 49-53. [PMID: 11547423]

3. Miyazawa, M., Shindo, M. and Shimada, T. Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica 31 (2001) 713-723. [PMID: 11695850]

[EC 1.14.14.56 created 2012 as EC 1.14.13.157, transferred 2017 to EC 1.14.14.56, modified 2018]

EC 1.14.14.73

Accepted name: albendazole monooxygenase (sulfoxide-forming)

Reaction: (1) albendazole + [reduced NADPH—hemoprotein reductase] + O2 = albendazole S-oxide + [oxidized NADPH—hemoprotein reductase] + H2O
(2) fenbendazole + [reduced NADPH—hemoprotein reductase] + O2 = fenbendazole S-oxide + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
fenbendazole = methyl [5-(phenylsulfanyl)-1H-benzimidazol-2-yl]carbamate

Other name(s): albendazole sulfoxidase (ambiguous); albendazole hydroxylase (ambiguous); CYP3A4 (gene name); CYP2J2 (gene name); CYP1A2 (gene name)

Systematic name: albendazole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (sulfoxide-forming)

Comments: This is one of the activities carried out by some microsomal cytochrome P-450 monooxygenases. A similar conversion is also carried out by a different microsomal enzyme (EC 1.14.13.32, albendazole monooxygenase (flavin-containing)), but it is estimated that cytochrome P-450s are responsible for 70% of the activity.

References:

1. Moroni, P., Buronfosse, T., Longin-Sauvageon, C., Delatour, P. and Benoit, E. Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes. Drug Metab. Dispos. 23 (1995) 160-165. [PMID: 7736906]

2. Rawden, H.C., Kokwaro, G.O., Ward, S.A. and Edwards, G. Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes. Br. J. Clin. Pharmacol. 49 (2000) 313-322. [PMID: 10759686]

3. Asteinza, J., Camacho-Carranza, R., Reyes-Reyes, R.E., Dorado-Gonzalez, V., V. and Espinosa-Aguirre, J.J. Induction of cytochrome P450 enzymes by albendazole treatment in the rat. Environ Toxicol Pharmacol 9 (2000) 31-37. [PMID: 11137466]

4. Lee, C.A., Neul, D., Clouser-Roche, A., Dalvie, D., Wester, M.R., Jiang, Y., Jones, J.P., 3rd, Freiwald, S., Zientek, M. and Totah, R.A. Identification of novel substrates for human cytochrome P450 2J2. Drug Metab. Dispos. 38 (2010) 347-356. [PMID: 19923256]

5. Wu, Z., Lee, D., Joo, J., Shin, J.H., Kang, W., Oh, S., Lee, D.Y., Lee, S.J., Yea, S.S., Lee, H.S., Lee, T. and Liu, K.H. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. 57 (2013) 5448-5456. [PMID: 23959307]

[EC 1.14.14.73 created 2018]

EC 1.14.14.74

Accepted name: albendazole monooxygenase (hydroxylating)

Reaction: albendazole + [reduced NADPH—hemoprotein reductase] + O2 = hydroxyalbendazole + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate
hydroxyalbendazole = methyl [5-(3-hydroxypropylsulfanyl)-1H-benzimidazol-2-yl]carbamate

Other name(s): CYP2J2 (gene name)

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

Comments: CYP2J2 is a microsomal cytochrome P-450 monooxygenase that catalyses the hydroxylation of the terminal carbon of the propylsulfanyl chain in albendazole, a broad-spectrum anthelmintic used against gastrointestinal nematodes and the larval stages of cestodes. cf. EC 1.14.14.73, albendazole monooxygenase (sulfoxide-forming).

References:

1. Wu, Z., Lee, D., Joo, J., Shin, J.H., Kang, W., Oh, S., Lee, D.Y., Lee, S.J., Yea, S.S., Lee, H.S., Lee, T. and Liu, K.H. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. 57 (2013) 5448-5456. [PMID: 23959307]

[EC 1.14.14.74 created 2018]

EC 1.14.14.75

Accepted name: fenbendazole monooxygenase (4'-hydroxylating)

Reaction: fenbendazole + [reduced NADPH—hemoprotein reductase] + O2 = 4'-hydroxyfenbendazole + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: fenbendazole = methyl [5-(phenylsulfanyl)-1H-benzimidazol-2-yl]carbamate
4'-hydroxyfenbendazole = methyl [5-(4-hydroxyphenylsulfanyl)-1H-benzimidazol-2-yl]carbamate
albendazole = methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate

Other name(s): CYP2C19 (gene name)

Systematic name: fenbendazole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (4'-hydroxylating)

Comments: CYP2C19 is microsomal cytochrome P-450 monooxygenase that catalyses the hydroxylation of the benzene ring of fenbendazole, a broad-spectrum anthelmintic used against gastrointestinal nematodes and the larval stages of cestodes. This activity is also carried out by CYP2J2. cf. EC 1.14.14.74, albendazole monooxygenase (hydroxylating). CYP2C19 does not act on albendazole.

References:

1. Wu, Z., Lee, D., Joo, J., Shin, J.H., Kang, W., Oh, S., Lee, D.Y., Lee, S.J., Yea, S.S., Lee, H.S., Lee, T. and Liu, K.H. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. 57 (2013) 5448-5456. [PMID: 23959307]

[EC 1.14.14.75 created 2018]

EC 1.14.14.76

Accepted name: ent-isokaurene C2/C3-hydroxylase

Reaction: ent-isokaurene + 2 O2 + 2 [reduced NADPH—hemoprotein reductase] = ent-isokaurene-2β,3β-diol + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) ent-isokaurene + O2 + [reduced NADPH—hemoprotein reductase] = ent-isokauren-2β-ol + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) ent-isokauren-2β-ol + O2 + [reduced NADPH—hemoprotein reductase] = ent-isokaurene-2β,3β-diol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Other name(s): CYP71Z6; ent-isokaurene C2-hydroxylase

Systematic name: ent-isokaurene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ent-isokaurene-2β,3β-diol forming)

Comments: This cytochrome P-450 (heme thiolate) enzyme has been characterized from the plant Oryza sativa (rice). It may be involved in production of oryzadione.

References:

1. Wu, Y., Hillwig, M.L., Wang, Q. and Peters, R.J. Parsing a multifunctional biosynthetic gene cluster from rice: biochemical characterization of CYP71Z6 & 7. FEBS Lett. 585 (2011) 3446-3451. [PMID: 21985968]

2. Kitaoka, N., Wu, Y., Xu, M. and Peters, R.J. Optimization of recombinant expression enables discovery of novel cytochrome P450 activity in rice diterpenoid biosynthesis. Appl. Microbiol. Biotechnol. 99 (2015) 7549-7558. [PMID: 25758958]

[EC 1.14.14.76 created 2012 as EC 1.14.13.143, transferred 2018 to EC 1.14.14.76]

EC 1.14.14.77

Accepted name: phenylacetonitrile α-monooxygenase

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

Other name(s): CYP3201B1 (gene name)

Systematic name: phenylacetonitrile,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase [(R)-mandelonitrile-forming]

Comments: The enzyme has been characterized from the cyanogenic millipede Chamberlinius hualienensis. Unlike plant enzymes that can catalyse this reaction (EC 1.14.14.44, phenylacetaldehyde oxime monooxygenase), this enzyme cannot act on phenylacetaldehyde oximes. It can accept (4-hydroxyphenyl)acetonitrile, (2-methylphenyl)acetonitrile, and (3-methylphenyl)acetonitrile as substrates at a lower rate.

References:

1. Yamaguchi, T., Kuwahara, Y. and Asano, Y. A novel cytochrome P450, CYP3201B1, is involved in (R)-mandelonitrile biosynthesis in a cyanogenic millipede. FEBS Open Bio 7 (2017) 335-347. [PMID: 28286729]

[EC 1.14.14.77 created 2018]

EC 1.14.14.78

Accepted name: phylloquinone ω-hydroxylase

Reaction: phylloquinone + [reduced NADPH—hemoprotein reductase] + O2 = ω-hydroxyphylloquinone + [oxidized NADPH—hemoprotein reductase] + H2O

Other name(s): vitamin K1 ω-hydroxylase; CYP4F2; CYP4F11

Systematic name: phylloquinone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxyphylloquinone forming)

Comments: A cytochrome P-450 (heme-thiolate) protein. Isolated from human tissue. The enzyme will also act on menaquinone-4. Prolonged action of CYP4F2, but not CYP4F11, on the ω hydroxyl group oxidizes it to the corresponding carboxylic acid. CYP4F2 also oxidizes leukotriene B4; see EC 1.14.13.30, leukotriene-B4 20-monooxygenase [1].

References:

1. Jin, R., Koop, D.R., Raucy, J.L. and Lasker, J.M. Role of human CYP4F2 in hepatic catabolism of the proinflammatory agent leukotriene B4. Arch. Biochem. Biophys. 359 (1998) 89-98. [PMID: 9799565]

2. Tang, Z., Salamanca-Pinzon, S.G., Wu, Z.L., Xiao, Y. and Guengerich, F.P. Human cytochrome P450 4F11: heterologous expression in bacteria, purification, and characterization of catalytic function. Arch. Biochem. Biophys. 494 (2010) 86-93. [PMID: 19932081]

3. Edson, K.Z., Prasad, B., Unadkat, J.D., Suhara, Y., Okano, T., Guengerich, F.P. and Rettie, A.E. Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. Biochemistry 52 (2013) 8276-8285. [PMID: 24138531]

[EC 1.14.14.78 created 2014 as EC 1.14.13.194, transferred 2018 to EC 1.14.14.78]

EC 1.14.14.79

Accepted name: docosahexaenoic acid ω-hydroxylase

Reaction: docosahexaenoate + [reduced NADPH—hemoprotein reductase] + O2 = 22-hydroxydocosahexaenoate + [oxidized NADPH—hemoprotein reductase] + H2O

Glossary: docosahexaenoate = (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoate
icosapentaenoate = (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate

Other name(s): CYP4F3B; CYP4V2; docosahexaenoate,NADPH:O2 oxidoreductase (22-hydroxydocosahexaenoate forming)

Systematic name: docosahexaenoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (22-hydroxydocosahexaenoate forming)

Comments: A cytochrome P-450 (heme-thiolate) protein isolated from human eye tissue. Defects in the enzyme are associated with Bietti crystalline corneoretinal dystrophy. The enzyme also produces some 21-hydroxydocosahexaenoate. Acts in a similar way on icosapentaenoic acid.

References:

1. Nakano, M., Kelly, E.J., Wiek, C., Hanenberg, H. and Rettie, A.E. CYP4V2 in Bietti’s crystalline dystrophy: ocular localization, metabolism of ω-3-polyunsaturated fatty acids, and functional deficit of the p.H331P variant. Mol. Pharmacol. 82 (2012) 679-686. [PMID: 22772592]

[EC 1.14.14.79 created 2014 as EC 1.14.13.199, transferred 2018 to EC 1.14.14.79]

EC 1.14.14.80

Accepted name: long-chain fatty acid ω-monooxygenase

Reaction: a long-chain fatty acid + [reduced NADPH—hemoprotein reductase] + O2 = an ω-hydroxy-long-chain fatty acid + [oxidized NADPH—hemoprotein reductase] + H2O

Other name(s): CYP704B1 (gene name); CYP52M1 (gene name); CYP4A (gene name); CYP86A (gene name)

Systematic name: long-chain fatty acid,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxylating)

Comments: A cytochrome P-450 (heme thiolate) enzyme. The plant enzyme CYP704B1, which is involved in the synthesis of sporopollenin, a complex polymer found at the outer layer of spores and pollen, acts on palmitate (18:0), stearate (18:0) and oleate (18:1). The plant enzyme CYP86A1 also acts on laurate (12:0). The enzyme from the yeast Starmerella bombicola (CYP52M1) acts on C16 to C20 saturated and unsaturated fatty acids and can also hydroxylate the (ω-1) position. The mammalian enzyme CYP4A acts on laurate (12:0), myristate (14:0), palmitate (16:0), oleate (18:1), and arachidonate (20:4).

References:

1. Benveniste, I., Tijet, N., Adas, F., Philipps, G., Salaun, J.P. and Durst, F. CYP86A1 from Arabidopsis thaliana encodes a cytochrome P450-dependent fatty acid ω-hydroxylase. Biochem. Biophys. Res. Commun. 243 (1998) 688-693. [PMID: 9500987]

2. Hoch, U., Zhang, Z., Kroetz, D.L. and Ortiz de Montellano, P.R. Structural determination of the substrate specificities and regioselectivities of the rat and human fatty acid ω-hydroxylases. Arch. Biochem. Biophys. 373 (2000) 63-71. [PMID: 10620324]

3. Dobritsa, A.A., Shrestha, J., Morant, M., Pinot, F., Matsuno, M., Swanson, R., Møller, B.L. and Preuss, D. CYP704B1 is a long-chain fatty acid ω-hydroxylase essential for sporopollenin synthesis in pollen of Arabidopsis. Plant Physiol. 151 (2009) 574-589. [PMID: 19700560]

4. Huang, F.C., Peter, A. and Schwab, W. Expression and characterization of CYP52 genes involved in the biosynthesis of sophorolipid and alkane metabolism from Starmerella bombicola. Appl. Environ. Microbiol. 80 (2014) 766-776. [PMID: 24242247]

[EC 1.14.14.80 created 2015 as EC 1.14.13.205, transferred 2018 to EC 1.14.14.80]

EC 1.14.14.81

Accepted name: flavanoid 3',5'-hydroxylase

Reaction: a flavanone + 2 [reduced NADPH—hemoprotein reductase] + 2 O2 = a 3',5'-dihydroxyflavanone + 2 [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) a flavanone + [reduced NADPH—hemoprotein reductase] + O2 = a 3'-hydroxyflavanone + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) a 3'-hydroxyflavanone + [reduced NADPH—hemoprotein reductase] + O2 = a 3',5'-dihydroxyflavanone + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here or click here or click here.

Other name(s): flavonoid 3',5'-hydroxylase

Systematic name: flavanone,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (3',5'-dihydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein found in plants. The 3',5'-dihydroxyflavanone is formed via the 3'-hydroxyflavanone. In Petunia hybrida the enzyme acts on naringenin, eriodictyol, dihydroquercetin (taxifolin) and dihydrokaempferol (aromadendrin). The enzyme catalyses the hydroxylation of 5,7,4'-trihydroxyflavanone (naringenin) at either the 3' position to form eriodictyol or at both the 3' and 5' positions to form 5,7,3',4',5'-pentahydroxyflavanone (dihydrotricetin). The enzyme also catalyses the hydroxylation of 3,5,7,3',4'-pentahydroxyflavanone (taxifolin) at the 5' position, forming ampelopsin.

References:

1. Menting, J., Scopes, R.K. and Stevenson, T.W. Characterization of flavonoid 3',5'-hydroxylase in microsomal membrane fraction of Petunia hybrida flowers. Plant Physiol. 106 (1994) 633-642. [PMID: 12232356]

2. Shimada, Y., Nakano-Shimada, R., Ohbayashi, M., Okinaka, Y., Kiyokawa, S. and Kikuchi, Y. Expression of chimeric P450 genes encoding flavonoid-3', 5'-hydroxylase in transgenic tobacco and petunia plants1. FEBS Lett. 461 (1999) 241-245. [PMID: 10567704]

3. de Vetten, N., ter Horst, J., van Schaik, H.P., de Boer, A., Mol, J. and Koes, R. A cytochrome b5 is required for full activity of flavonoid 3', 5'-hydroxylase, a cytochrome P450 involved in the formation of blue flower colors. Proc. Natl. Acad. Sci. USA 96 (1999) 778-783. [PMID: 9892710]

[EC 1.14.14.81 created 2004 as EC 1.14.13.88, transferred 2018 to EC 1.14.14.81]

EC 1.14.14.82

Accepted name: flavonoid 3'-monooxygenase

Reaction: a flavonoid + [reduced NADPH—hemoprotein reductase] + O2 = a 3'-hydroxyflavonoid + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here or click here.

Other name(s): CYP75B1 (gene name); flavonoid 3'-hydroxylase; flavonoid 3-hydroxylase (incorrect); NADPH:flavonoid-3'-hydroxylase (incorrect); flavonoid 3-monooxygenase (incorrect)

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

Comments: A cytochrome P-450 (heme-thiolate) protein found in plants. Acts on a number of flavonoids, including the flavanone naringenin and the flavone apigenin. Does not act on 4-coumarate or 4-coumaroyl-CoA.

References:

1. Forkmann, G., Heller, W. and Grisebach, H. Anthocyanin biosynthesis in flowers of Matthiola incana flavanone 3- and flavonoid 3'-hydroxylases. Z. Naturforsch. C: Biosci. 35 (1980) 691-695.

2. Brugliera, F., Barri-Rewell, G., Holton, T.A. and Mason, J.G. Isolation and characterization of a flavonoid 3'-hydroxylase cDNA clone corresponding to the Ht1 locus of Petunia hybrida. Plant J. 19 (1999) 441-451. [PMID: 10504566]

3. Schoenbohm, C., Martens, S., Eder, C., Forkmann, G. and Weisshaar, B. Identification of the Arabidopsis thaliana flavonoid 3'-hydroxylase gene and functional expression of the encoded P450 enzyme. Biol. Chem. 381 (2000) 749-753. [PMID: 11030432]

[EC 1.14.14.82 created 1983 as EC 1.14.13.21, transferred 2018 to EC 1.14.14.82]

EC 1.14.14.83

Accepted name: geraniol 8-hydroxylase

Reaction: geraniol + [reduced NADPH—hemoprotein reductase] + O2 = (6E)-8-hydroxygeraniol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Other name(s): CYP76B6 (gene name); G10H (gene name)

Systematic name: geraniol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8-hydroxylating)

Comments: A cytochrome P-450 (heme thiolate) protein found in plants. Also hydroxylates nerol and citronellol, cf. EC 1.14.14.84, linalool 8-monooxygenase. The recommended numbering of geraniol gives 8-hydroxygeraniol as the product rather than 10-hydroxygeraniol as used by references 1-3. See prenol nomenclature Pr-1. The cloned enzyme also catalysed, but less efficiently, the 3'-hydroxylation of naringenin (cf. EC 1.14.14.82, flavonoid 3'-monooxygenase) [3].

References:

1. Collu, G., Unver, N., Peltenburg-Looman, A.M., van der Heijden, R., Verpoorte, R. and Memelink, J. Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett. 508 (2001) 215-220. [PMID: 11718718]

2. Wang, J., Liu, Y., Cai, Y., Zhang, F., Xia, G. and Xiang, F. Cloning and functional analysis of geraniol 10-hydroxylase, a cytochrome P450 from Swertia mussotii Franch. Biosci. Biotechnol. Biochem. 74 (2010) 1583-1590. [PMID: 20699579]

3. Sung, P.H., Huang, F.C., Do, Y.Y. and Huang, P.L. Functional expression of geraniol 10-hydroxylase reveals its dual function in the biosynthesis of terpenoid and phenylpropanoid. J. Agric. Food Chem. 59 (2011) 4637-4643. [PMID: 21504162]

[EC 1.14.14.83 created 2012 as EC 1.14.13.152, transferred 2018 to EC 1.14.14.83]

EC 1.14.14.84

Accepted name: linalool 8-monooxygenase

Reaction: linalool + 2 [reduced NADPH—hemoprotein reductase] + 2 O2 = (6E)-8-oxolinalool + 2 [oxidized NADPH—hemoprotein reductase] + 3 H2O (overall reaction)
(1a) linalool + [reduced NADPH—hemoprotein reductase] + O2 = (6E)-8-hydroxylinalool + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) (6E)-8-hydroxylinalool + [reduced NADPH—hemoprotein reductase] + O2 = (6E)-8-oxolinalool + [oxidized NADPH—hemoprotein reductase] + 2 H2O

For diagram of reaction click here.

Glossary: linalool = 3,7-dimethylocta-1,6-dien-3-ol

Other name(s): P-450lin; CYP111

Systematic name: linalool,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (8-hydroxylating)

Comments: A cytochrome P-450 (heme-thiolate) protein found in plants. The secondary electron donor is a specific [2Fe-2S] ferredoxin from the same bacterial strain.

References:

1. Ullah, A.J., Murray, R.I., Bhattacharyya, P.K., Wagner, G.C. and Gunsalus, I.C. Protein components of a cytochrome P-450 linalool 8-methyl hydroxylase. J. Biol. Chem. 265 (1990) 1345-1351. [PMID: 2295633]

2. Ropp, J.D., Gunsalus, I.C. and Sligar, S.G. Cloning and expression of a member of a new cytochrome P-450 family: cytochrome P-450lin (CYP111) from Pseudomonas incognita. J. Bacteriol. 175 (1993) 6028-6037. [PMID: 8376348]

[EC 1.14.14.84 created 1989 as EC 1.14.99.28, transferred 2012 to EC 1.14.13.151, transferred 2018 to EC 1.14.14.84]

EC 1.14.14.85

Accepted name: 7-deoxyloganin 7-hydroxylase

Reaction: 7-deoxyloganin + [reduced NADPH—hemoprotein reductase] + O2 = loganin + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

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

Comments: A cytochrome P-450 (heme-thiolate) protein found in plants.

References:

1. Katano, N., Yamamoto, H., Iio, R. and Inoue, K. 7-Deoxyloganin 7-hydroxylase in Lonicera japonica cell cultures. Phytochemistry 58 (2001) 53-58. [PMID: 11524113]

[EC 1.14.14.85 created 2002 as EC 1.14.13.74, transferred 2018 to EC 1.14.14.85]

EC 1.14.14.86

Accepted name: ent-kaurene monooxygenase

Reaction: ent-kaur-16-ene + 3 [reduced NADPH—hemoprotein reductase] + 3 O2 = ent-kaur-16-en-19-oate + 3 [oxidized NADPH—hemoprotein reductase] + 4 H2O (overall reaction)
(1a) ent-kaur-16-ene + [reduced NADPH—hemoprotein reductase] + O2 = ent-kaur-16-en-19-ol + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) ent-kaur-16-en-19-ol + [reduced NADPH—hemoprotein reductase] + O2 = ent-kaur-16-en-19-al + [oxidized NADPH—hemoprotein reductase] + 2 H2O
(1c) ent-kaur-16-en-19-al + [reduced NADPH—hemoprotein reductase] + O2 = ent-kaur-16-en-19-oate + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Other name(s): ent-kaurene oxidase (misleading)

Systematic name: ent-kaur-16-ene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating)

Comments: A cytochrome P-450 (heme thiolate) protein found in plants. Catalyses three successive oxidations of the 4-methyl group of ent-kaurene giving kaurenoic acid.

References:

1. Ashman, P.J., Mackenzie, A. and Bramley, P.M. Characterization of ent-kaurene oxidase activity from Gibberella fujikuroi. Biochim. Biophys. Acta 1036 (1990) 151-157. [PMID: 2223832]

2. Archer, C., Ashman, P.J., Hedden, P., Bowyer, J.R. and Bramley, P.M. Purification of ent-kaurene oxidase from Gibberella fujikuroi and Cucurbita maxima. Biochem. Soc. Trans. 20 (1992) 218. [PMID: 1397591]

3. Helliwell, C.A., Poole, A., Peacock, W.J. and Dennis, E.S. Arabidopsis ent-kaurene oxidase catalyzes three steps of gibberellin biosynthesis. Plant Physiol. 119 (1999) 507-510. [PMID: 9952446]

[EC 1.14.14.86 created 2002 as EC 1.14.13.78, transferred 2018 to EC 1.14.14.86]

EC 1.14.14.87

Accepted name: 2-hydroxyisoflavanone synthase

Reaction: (1) liquiritigenin + O2 + [reduced NADPH—hemoprotein reductase] = 2,4',7-trihydroxyisoflavanone + H2O + [oxidized NADPH—hemoprotein reductase]
(2) (2S)-naringenin + O2 + [reduced NADPH—hemoprotein reductase] = 2,4',5,7-tetrahydroxyisoflavanone + H2O + [oxidized NADPH—hemoprotein reductase]

For diagram of reaction click here.

Glossary: liquiritigenin = 4',7-dihydroxyflavanone
(2S)-naringenin = 4',5,7-dihydroxyflavanone
2,4',5,7-tetrahydroxyisoflavanone = 2-hydroxy-2,3-dihydrogenistein

Other name(s): CYP93C; IFS; isoflavonoid synthase

Systematic name: liquiritigenin, [reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hydroxylating, aryl migration)

Comments: A cytochrome P-450 (heme thiolate) protein found in plants. The reaction involves the migration of the 2-phenyl group of the flavanone to the 3-position of the isoflavanone. The 2-hydroxyl group is derived from the oxygen molecule. EC 4.2.1.105, 2-hydroxyisoflavanone dehydratase, acts on the products with loss of water and formation of genistein and daidzein, respectively.

References:

1. Kochs, G. and Grisebach, H. Enzymic synthesis of isoflavones. Eur. J. Biochem. 155 (1986) 311-318. [PMID: 3956488]

2. Hashim, M.F., Hakamatsuka, T., Ebizuka, Y. and Sankawa, U. Reaction mechanism of oxidative rearrangement of flavanone in isoflavone biosynthesis. FEBS Lett. 271 (1990) 219-222. [PMID: 2226805]

3. Steele, C. L., Gijzen, M., Qutob, D. and Dixon, R.A. Molecular characterization of the enzyme catalyzing the aryl migration reaction of isoflavonoid biosynthesis in soybean. Arch. Biochem. Biophys. 367 (1999) 146-150. [PMID: 10375412]

4. Sawada, Y., Kinoshita, K., Akashi, T., Aoki, T. and Ayabe, S. Key amino acid residues required for aryl migration catalysed by the cytochrome P450 2-hydroxyisoflavanone synthase. Plant J. 31 (2002) 555-564. [PMID: 12207646]

5. Sawada, Y. and Ayabe, S. Multiple mutagenesis of P450 isoflavonoid synthase reveals a key active-site residue. Biochem. Biophys. Res. Commun. 330 (2005) 907-913. [PMID: 15809082]

[EC 1.14.14.87 created 2011 as EC 1.14.13.136, modified 2013, transferred 2018 to EC 1.14.14.87]

EC 1.14.15.27

Accepted name: β-dihydromenaquinone-9 ω-hydroxylase

Reaction: β-dihydromenaquinone-9 + 2 reduced ferredoxin [iron-sulfur] cluster + O2 = ω-hydroxy-β-dihydromenaquinone-9 + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Glossary: β-dihydromenaquinone-9 = MK-9(II-H2) = 2-methyl-3-[(2E,10E,14E,18E,22E,26E,30E,33E)-3,7,11,15,19,23,27,31,35-nonamethylhexatriaconta-2,10,14,18,22,26,30,33-octaen-1-yl]naphthalene-1,4-dione

Other name(s): cyp128 (gene name)

Systematic name: β-dihydromenaquinone-9,reduced ferredoxin:oxygen oxidoreductase (ω-hydroxylating)

Comments: The bacterial cytochrome P-450 enzyme is involved in the biosynthesis of ω-sulfo-β-dihydromenaquinone-9 by members of the Mycobacterium tuberculosis complex.

References:

1. Holsclaw, C.M., Sogi, K.M., Gilmore, S.A., Schelle, M.W., Leavell, M.D., Bertozzi, C.R. and Leary, J.A. Structural characterization of a novel sulfated menaquinone produced by stf3 from Mycobacterium tuberculosis. ACS Chem. Biol. 3 (2008) 619-624. [PMID: 18928249]

2. Sogi, K.M., Holsclaw, C.M., Fragiadakis, G.K., Nomura, D.K., Leary, J.A. and Bertozzi, C.R. Biosynthesis and regulation of sulfomenaquinone, a metabolite associated with virulence in Mycobacterium tuberculosis. ACS Infect Dis 2 (2016) 800-806. [PMID: 27933784]

[EC 1.14.15.27 created 2018]

EC 1.14.15.28

Accepted name: cholest-4-en-3-one 26-monooxygenase [(25R)-3-oxocholest-4-en-26-oate forming]

Reaction: cholest-4-en-3-one + 6 reduced [2Fe-2S] ferredoxin + 3 O2 = (25R)-3-oxocholest-4-en-26-oate + 6 oxidized [2Fe-2S] ferredoxin + 4 H2O (overall reaction)
(1a) cholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-26-hydroxycholest-4-en-3-one + 2 oxidized [2Fe-2S] ferredoxin + H2O
(1b) (25R)-26-hydroxycholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-26-oxocholest-4-en-3-one + 2 oxidized [2Fe-2S] ferredoxin + 2 H2O
(1c) (25R)-26-oxocholest-4-en-3-one + 2 reduced [2Fe-2S] ferredoxin + O2 = (25R)-3-oxocholest-4-en-26-oate + 2 oxidized [2Fe-2S] ferredoxin + H2O

Other name(s): CYP142

Systematic name: cholest-4-en-3-one,reduced [2Fe-2S] ferredoxin:oxygen oxidoreductase [(25R)-3-oxocholest-4-en-26-oate forming]

Comments: This cytochrome P-450 (heme-thiolate) enzyme, found in several bacterial pathogens, is involved in degradation of the host cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol. The products are exclusively in the (25R) conformation. The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.29, cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]. The enzyme can receive electrons from ferredoxin reductase in vitro, its natural electron donor is not known yet.

References:

1. Driscoll, M.D., McLean, K.J., Levy, C., Mast, N., Pikuleva, I.A., Lafite, P., Rigby, S.E., Leys, D. and Munro, A.W. Structural and biochemical characterization of Mycobacterium tuberculosis CYP142: evidence for multiple cholesterol 27-hydroxylase activities in a human pathogen. J. Biol. Chem. 285 (2010) 38270-38282. [PMID: 20889498]

2. Johnston, J.B., Ouellet, H. and Ortiz de Montellano, P.R. Functional redundancy of steroid C26-monooxygenase activity in Mycobacterium tuberculosis revealed by biochemical and genetic analyses. J. Biol. Chem. 285 (2010) 36352-36360. [PMID: 20843794]

[EC 1.14.15.28 created 2016 as EC 1.14.13.221, transferred 2018 to EC 1.14.15.28]

EC 1.14.15.29

Accepted name: cholest-4-en-3-one 26-monooxygenase [(25S)-3-oxocholest-4-en-26-oate forming]

Reaction: cholest-4-en-3-one + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2 = (25S)-3-oxocholest-4-en-26-oate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O (overall reaction)
(1a) cholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-hydroxycholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) (25S)-26-hydroxycholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-26-oxocholest-4-en-3-one + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(1c) (25S)-26-oxocholest-4-en-3-one + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = (25S)-3-oxocholest-4-en-26-oate + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Other name(s): CYP125; CYP125A1; cholest-4-en-3-one 27-monooxygenase (misleading); cholest-4-en-3-one,NADH:oxygen oxidoreductase (26-hydroxylating); cholest-4-en-3-one 26-monooxygenase (ambiguous)

Systematic name: cholest-4-en-3-one,[reduced ferredoxin]:oxygen oxidoreductase [(25S)-3-oxocholest-4-en-26-oate forming]

Comments: A cytochrome P-450 (heme-thiolate) protein found in several bacterial pathogens. The enzyme is involved in degradation of the host’s cholesterol. It catalyses the hydroxylation of the C-26 carbon, followed by oxidation of the alcohol to the carboxylic acid via the aldehyde intermediate, initiating the degradation of the alkyl side-chain of cholesterol [4]. The products are exclusively in the (25S) configuration. The enzyme is part of a two-component system that also includes a ferredoxin reductase (most likely KshB, which also interacts with EC 1.14.15.30, 3-ketosteroid 9α-monooxygenase). The enzyme also accepts cholesterol as a substrate. cf. EC 1.14.15.28, cholest-4-en-3-one 27-monooxygenase.

References:

1. Rosloniec, K.Z., Wilbrink, M.H., Capyk, J.K., Mohn, W.W., Ostendorf, M., van der Geize, R., Dijkhuizen, L. and Eltis, L.D. Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in Rhodococcus jostii RHA1. Mol. Microbiol. 74 (2009) 1031-1043. [PMID: 19843222]

2. McLean, K.J., Lafite, P., Levy, C., Cheesman, M.R., Mast, N., Pikuleva, I.A., Leys, D. and Munro, A.W. The Structure of Mycobacterium tuberculosis CYP125: molecular basis for cholesterol binding in a P450 needed for host infection. J. Biol. Chem. 284 (2009) 35524-35533. [PMID: 19846552]

3. Capyk, J.K., Kalscheuer, R., Stewart, G.R., Liu, J., Kwon, H., Zhao, R., Okamoto, S., Jacobs, W.R., Jr., Eltis, L.D. and Mohn, W.W. Mycobacterial cytochrome P450 125 (Cyp125) catalyzes the terminal hydroxylation of C27 steroids. J. Biol. Chem. 284 (2009) 35534-35542. [PMID: 19846551]

4. Ouellet, H., Guan, S., Johnston, J.B., Chow, E.D., Kells, P.M., Burlingame, A.L., Cox, J.S., Podust, L.M. and de Montellano, P.R. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol. Microbiol. 77 (2010) 730-742. [PMID: 20545858]

[EC 1.14.15.29 created 2012 as EC 1.14.13.141, modified 2016, transferred 2018 to EC 1.14.15.29]

EC 1.14.15.30

Accepted name: 3-ketosteroid 9α-monooxygenase

Reaction: androsta-1,4-diene-3,17-dione + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = 9α-hydroxyandrosta-1,4-diene-3,17-dione + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O

Other name(s): KshA; 3-ketosteroid 9α-hydroxylase

Systematic name: androsta-1,4-diene-3,17-dione,[reduced ferredoxin]:oxygen oxidoreductase (9α-hydroxylating)

Comments: The enzyme is involved in the cholesterol degradation pathway of several bacterial pathogens, such as Mycobacterium tuberculosis. It forms a two-component system with a ferredoxin reductase (KshB). The enzyme contains a Rieske-type iron-sulfur center and non-heme iron. The product of the enzyme is unstable, and spontaneously converts to 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione.

References:

1. Petrusma, M., Dijkhuizen, L. and van der Geize, R. Rhodococcus rhodochrous DSM 43269 3-ketosteroid 9α-hydroxylase, a two-component iron-sulfur-containing monooxygenase with subtle steroid substrate specificity. Appl. Environ. Microbiol. 75 (2009) 5300-5307. [PMID: 19561185]

2. Capyk, J.K., D'Angelo, I., Strynadka, N.C. and Eltis, L.D. Characterization of 3-ketosteroid 9α-hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of Mycobacterium tuberculosis. J. Biol. Chem. 284 (2009) 9937-9946. [PMID: 19234303]

3. Capyk, J.K., Casabon, I., Gruninger, R., Strynadka, N.C. and Eltis, L.D. Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis. J. Biol. Chem. 286 (2011) 40717-40724. [PMID: 21987574]

[EC 1.14.15.30 created 2012 as EC 1.14.13.142, transferred 2018 to EC 1.14.15.30]

EC 1.14.19.61

Accepted name: dihydrorhizobitoxine desaturase

Reaction: dihydrorhizobitoxine + 2 reduced ferredoxin [iron-sulfur] cluster + O2 + 2 H+ = rhizobitoxine + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O

Glossary: dihydrorhizobitoxine = (2S)-2-amino-4-[(2R)-2-amino-3-hydroxypropoxy]butanoate
rhizobitoxine = (2S,3E)-2-amino-4-[(2R)-2-amino-3-hydroxypropoxy]but-3-enoate

Other name(s): rtxC (gene name)

Systematic name: dihydrorhizobitoxine,ferredoxin:oxygen oxidoreductase (3,4 trans-dehydrogenating)

Comments: The enzyme, characterized from the bacterium Bradyrhizobium elkanii, catalyses the final step in the biosynthesis of the nodulation enhancer compound rhizobitoxine.

References:

1. Yasuta, T., Okazaki, S., Mitsui, H., Yuhashi, K., Ezura, H. and Minamisawa, K. DNA sequence and mutational analysis of rhizobitoxine biosynthesis genes in Bradyrhizobium elkanii. Appl. Environ. Microbiol. 67 (2001) 4999-5009. [PMID: 11679318]

2. Okazaki, S., Sugawara, M. and Minamisawa, K. Bradyrhizobium elkanii rtxC gene is required for expression of symbiotic phenotypes in the final step of rhizobitoxine biosynthesis. Appl. Environ. Microbiol. 70 (2004) 535-541. [PMID: 14711685]

[EC 1.14.19.61 created 2018]

EC 1.14.20.9

Accepted name: L-tyrosine isonitrile desaturase

Reaction: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = (2E)-3-(4-hydroxyphenyl)-2-isocyanoprop-2-enoate + succinate + CO2 + H2O

Glossary: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoic acid = L-tyrosine isonitrile
paerucumarin = 6,7-dihydroxy-3-isocyanochromen-2-one

Other name(s): pvcB (gene name)

Systematic name: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase

Comments: The enzyme is a member of the Fe2+, 2-oxoglutarate-dependent oxygenases and requires Fe2+. It has been characterized from bacteria that form the isonitrile-functionalized compound paerucumarin. cf. EC 1.14.20.10, L-tyrosine isonitrile desaturase/decarboxylase.

References:

1. Clarke-Pearson, M.F. and Brady, S.F. Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J. Bacteriol. 190 (2008) 6927-6930. [PMID: 18689486]

2. Drake, E.J. and Gulick, A.M. Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J. Mol. Biol. 384 (2008) 193-205. [PMID: 18824174]

3. Zhu, J., Lippa, G.M., Gulick, A.M. and Tipton, P.A. Examining reaction specificity in PvcB, a source of diversity in isonitrile-containing natural products. Biochemistry 54 (2015) 2659-2669. [PMID: 25866990]

[EC 1.14.20.9 created 2018]

EC 1.14.20.10

Accepted name: L-tyrosine isonitrile desaturase/decarboxylase

Reaction: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = 4-[(E)-2-isocyanoethenyl]phenol + succinate + 2 CO2 + H2O

Glossary: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoic acid = L-tyrosine isonitrile
rhabduscin = N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-{4-[(E)-2-isocyanoethenyl]phenoxy}-2-methyloxan-3-yl]acetamide

Other name(s): pvcB (gene name)

Systematic name: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating)

Comments: The enzyme, characterized from the bacterium Xenorhabdus nematophila, is involved in rhabduscin biosynthesis. The enzyme is a member of the Fe2+, 2-oxoglutarate-dependent oxygenases. It is similar to EC 1.14.20.9, L-tyrosine isonitrile desaturase. However, the latter does not catalyse a decarboxylation of the substrate.

References:

1. Crawford, J.M., Portmann, C., Zhang, X., Roeffaers, M.B. and Clardy, J. Small molecule perimeter defense in entomopathogenic bacteria. Proc. Natl Acad. Sci. USA 109 (2012) 10821-10826. [PMID: 22711807]

2. Zhu, J., Lippa, G.M., Gulick, A.M. and Tipton, P.A. Examining reaction specificity in PvcB, a source of diversity in isonitrile-containing natural products. Biochemistry 54 (2015) 2659-2669. [PMID: 25866990]

[EC 1.14.20.10 created 2018]

EC 1.14.20.11

Accepted name: 3-[(Z)-2-isocyanoethenyl]-1H-indole synthase

Reaction: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = 3-[(Z)-2-isocyanoethenyl]-1H-indole + succinate + 2 CO2 + H2O

Glossary: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile

Other name(s): ambI3 (gene name); famH3 (gene name)

Systematic name: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating, 3-[(Z)-2-isocyanoethenyl]-1H-indole-forming)

Comments: The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, participates in the biosynthesis of hapalindole-type alkaloids. The enzyme catalyses an Fe2+, 2-oxoglutarate-dependent monooxygenation at C-3, which is followed by decarboxylation and dehydration, resulting in the generation of a cis C-C double bond. cf. EC 1.14.20.12, L-tryptophan isonitrile desaturase/decarboxylase (3-[(E)-2-isocyanoethenyl]-1H-indole-forming).

References:

1. Hillwig, M.L., Zhu, Q. and Liu, X. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem. Biol. 9 (2014) 372-377. [PMID: 24180436]

2. Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208-1211. [PMID: 28212039]

[EC 1.14.20.11 created 2018]

EC 1.14.20.12

Accepted name: 3-[(E)-2-isocyanoethenyl]-1H-indole synthase

Reaction: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = 3-[(E)-2-isocyanoethenyl]-1H-indole + succinate + 2 CO2 + H2O

Glossary: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile

Other name(s): isnB (gene name)

Systematic name: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating, 3-[(E)-2-isocyanoethenyl]-1H-indole-forming)

Comments: The enzyme has been characterized from an unidentified soil bacterium. It catalyses an Fe2+, 2-oxoglutarate-dependent monooxygenation at C-3, which is followed by decarboxylation and dehydration, resulting in the generation of a trans C-C double bond. cf. EC 1.14.20.11, L-tryptophan isonitrile desaturase/decarboxylase (3-[(Z)-2-isocyanoethenyl]-1H-indole-forming).

References:

1. Brady, S.F. and Clardy, J. Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew Chem Int Ed Engl 44 (2005) 7063-7065. [PMID: 16206308]

2. Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208-1211. [PMID: 28212039]

[EC 1.14.20.12 created 2018]

EC 1.14.20.13

Accepted name: 6β-hydroxyhyoscyamine epoxidase

Reaction: (6S)-6β-hydroxyhyoscyamine + 2-oxoglutarate + O2 = scopolamine + succinate + CO2 + H2O

For diagram of reaction click here.

Glossary: scopolamine = hyoscine = (1R,2R,4S,5S,7s)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl (2S)-3-hydroxy-2-phenylpropanoate

Other name(s): hydroxyhyoscyamine dioxygenase; (6S)-6-hydroxyhyoscyamine,2-oxoglutarate oxidoreductase (epoxide-forming)

Systematic name: (6S)-6β-hydroxyhyoscyamine,2-oxoglutarate:oxygen oxidoreductase (epoxide-forming)

Comments: Requires Fe2+ and ascorbate.

References:

1. Hashimoto, T., Kohno, J. and Yamada, Y. 6β-Hydroxyhyoscyamine epoxidase from cultured roots of Hyoscyamus niger. Phytochemistry 28 (1989) 1077-1082.

[EC 1.14.20.13 created 1992 as EC 1.14.11.14, transferred 2018 to EC 1.14.20.13]

EC 1.14.99.60

Accepted name: 3-demethoxyubiquinol 3-hydroxylase

Reaction: 6-methoxy-3-methyl-2-(all-trans-polyprenyl)-1,4-benzoquinol + a reduced acceptor + O2 = 3-demethylubiquinol + acceptor + H2O

Glossary: 3-demethylubiquinol = 3-methoxy-6-methyl-5-(all trans-polyprenyl)benzene-1,2,4-triol

Other name(s): 6-methoxy-3-methyl-2-(all-trans-polyprenyl)-1,4-benzoquinol 5-hydroxylase; COQ7 (gene name); clk-1 (gene name); ubiF (gene name)

Systematic name: 6-methoxy-3-methyl-2-(all-trans-polyprenyl)-1,4-benzoquinol,acceptor:oxygen oxidoreductase (5-hydroxylating)

Comments: The enzyme catalyses the last hydroxylation reaction during the biosynthesis of ubiquinone.

References:

1. Marbois, B.N. and Clarke, C.F. The COQ7 gene encodes a protein in Saccharomyces cerevisiae necessary for ubiquinone biosynthesis. J. Biol. Chem. 271 (1996) 2995-3004. [PMID: 8621692]

2. Vajo, Z., King, L.M., Jonassen, T., Wilkin, D.J., Ho, N., Munnich, A., Clarke, C.F. and Francomano, C.A. Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging. Mamm Genome 10 (1999) 1000-1004. [PMID: 10501970]

3. Kwon, O., Kotsakis, A. and Meganathan, R. Ubiquinone (coenzyme Q) biosynthesis in Escherichia coli: identification of the ubiF gene. FEMS Microbiol. Lett. 186 (2000) 157-161. [PMID: 10802164]

4. Stenmark, P., Grunler, J., Mattsson, J., Sindelar, P.J., Nordlund, P. and Berthold, D.A. A new member of the family of di-iron carboxylate proteins. Coq7 (clk-1), a membrane-bound hydroxylase involved in ubiquinone biosynthesis. J. Biol. Chem. 276 (2001) 33297-33300. [PMID: 11435415]

5. Tran, U.C., Marbois, B., Gin, P., Gulmezian, M., Jonassen, T. and Clarke, C.F. Complementation of Saccharomyces cerevisiae coq7 mutants by mitochondrial targeting of the Escherichia coli UbiF polypeptide: two functions of yeast Coq7 polypeptide in coenzyme Q biosynthesis. J. Biol. Chem. 281 (2006) 16401-16409. [PMID: 16624818]

[EC 1.14.99.60 created 2018]

*EC 1.18.6.1

Accepted name: nitrogenase

Reaction: 8 reduced ferredoxin + 8 H+ + N2 + 16 ATP + 16 H2O = 8 oxidized ferredoxin + H2 + 2 NH3 + 16 ADP + 16 phosphate

For diagram of reaction click here.

Other name(s): reduced ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing)

Systematic name: ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing, molybdenum-dependent)

Comments: Requires Mg2+. The enzyme is a complex of two components (namely dinitrogen reductase and dinitrogenase). Dinitrogen reductase is a [4Fe-4S] protein, which, in the presence of two molecules of ATP, transfers an electron from ferredoxin to the dinitrogenase component. Dinitrogenase is a molybdenum-iron protein that reduces dinitrogen to two molecules of ammonia in three successive two-electron reductions via diazene and hydrazine. The reduction is initiated by formation of hydrogen in stoichiometric amounts [2]. Acetylene is reduced to ethylene (but only very slowly to ethane), azide to nitrogen and ammonia, and cyanide to methane and ammonia. In the absence of a suitable substrate, hydrogen is slowly formed. Ferredoxin may be replaced by flavodoxin [see EC 1.19.6.1 nitrogenase (flavodoxin)]. The enzyme does not reduce CO (cf. EC 1.18.6.2, vanadium-dependent nitrogenase).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, UM-BBD, CAS registry number: 9013-04-1

References:

1. Zumft, W.G., Paneque, A., Aparicio, P.J. and Losada, M. Mechanism of nitrate reduction in Chlorella. Biochem. Biophys. Res. Commun. 36 (1969) 980-986. [PMID: 4390523]

2. Liang, J. and Burris, R.H. Hydrogen burst associated with nitrogenase-catalyzed reactions. Proc. Natl. Acad. Sci. USA 85 (1988) 9446-9450. [PMID: 3200830]

3. Dance, I. The mechanism of nitrogenase. Computed details of the site and geometry of binding of alkyne and alkene substrates and intermediates. J. Am. Chem. Soc. 126 (2004) 11852-11863. [PMID: 15382920]

4. Chan, J.M., Wu, W., Dean, D.R. and Seefeldt, L.C. Construction and characterization of a heterodimeric iron protein: defining roles for adenosine triphosphate in nitrogenase catalysis. Biochemistry 39 (2000) 7221-7228. [PMID: 10852721]

[EC 1.18.6.1 created 1978 as EC 1.18.2.1, transferred 1984 to EC 1.18.6.1, modified 2005, modified 2018]

EC 1.18.6.2

Accepted name: vanadium-dependent nitrogenase

Reaction: 12 reduced ferredoxin + 12 H+ + N2 + 40 ATP + 40 H2O = 12 oxidized ferredoxin + 3 H2 + 2 NH3 + 40 ADP + 40 phosphate

Other name(s): vnfD (gene name); vnfG (gene name); vnfK (gene name)

Systematic name: ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing, vanadium-dependent)

Comments: Requires Mg2+. This enzyme, originally isolated from the bacterium Azotobacter vinelandii, is a complex of two components (namely dinitrogen reductase and dinitrogenase). Dinitrogen reductase is a [4Fe-4S] protein, which, in the presence of ATP, transfers an electron from ferredoxin to the dinitrogenase component. Dinitrogenase is a vanadium-iron protein that reduces dinitrogen to two molecules of ammonia in three successive two-electron reductions via diazine and hydrazine. Compared with molybdenum-depedent nitrogenase (EC 1.18.6.1), this enzyme produces more dihydrogen and consumes more ATP per dinitrogen molecule being reduced. Unlike EC 1.18.6.1, this enzyme can also use CO as substrate, producing ethene, ethane and propane [7,9].

References:

1. Eady, R.R., Richardson, T.H., Miller, R.W., Hawkins, M. and Lowe, D.J. The vanadium nitrogenase of Azotobacter chroococcum. Purification and properties of the Fe protein. Biochem. J. 256 (1988) 189-196. [PMID: 2851977]

2. Miller, R.W. and Eady, R.R. Molybdenum and vanadium nitrogenases of Azotobacter chroococcum. Low temperature favours N2 reduction by vanadium nitrogenase. Biochem. J. 256 (1988) 429-432. [PMID: 3223922]

3. Thorneley, R.N., Bergstrom, N.H., Eady, R.R. and Lowe, D.J. Vanadium nitrogenase of Azotobacter chroococcum. MgATP-dependent electron transfer within the protein complex. Biochem. J. 257 (1989) 789-794. [PMID: 2784670]

4. Dilworth, M.J., Eldridge, M.E. and Eady, R.R. Correction for creatine interference with the direct indophenol measurement of NH3 in steady-state nitrogenase assays. Anal. Biochem. 207 (1992) 6-10. [PMID: 1336937]

5. Dilworth, M.J., Eldridge, M.E. and Eady, R.R. The molybdenum and vanadium nitrogenases of Azotobacter chroococcum: effect of elevated temperature on N2 reduction. Biochem. J. 289 (1993) 395-400. [PMID: 8424785]

6. Eady, R.R. Current status of structure function relationships of vanadium nitrogenase. Coordinat. Chem. Rev. 237 (2003) 23-30.

7. Lee, C.C., Hu, Y. and Ribbe, M.W. Vanadium nitrogenase reduces CO. Science 329 (2010) 642. [PMID: 20689010]

8. Lee, C.C., Hu, Y. and Ribbe, M.W. Tracing the hydrogen source of hydrocarbons formed by vanadium nitrogenase. Angew Chem Int Ed Engl 50 (2011) 5545-5547. [PMID: 21538750]

9. Sippel, D. and Einsle, O. The structure of vanadium nitrogenase reveals an unusual bridging ligand. Nat. Chem. Biol. 13 (2017) 956-960. [PMID: 28692069]

[EC 1.18.6.2 created 2018]

*EC 2.3.1.74

Accepted name: chalcone synthase

Reaction: 3 malonyl-CoA + 4-coumaroyl-CoA = 4 CoA + naringenin chalcone + 3 CO2

For diagram of reaction click here.

Glossary: phloretin = 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one

Other name(s): naringenin-chalcone synthase; flavanone synthase; 6'-deoxychalcone synthase; chalcone synthetase; DOCS; CHS

Systematic name: malonyl-CoA:4-coumaroyl-CoA malonyltransferase (cyclizing)

Comments: The enzyme catalyses the first committed step in the biosynthesis of flavonoids. It can also act on dihydro-4-coumaroyl-CoA, forming phloretin.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 56803-04-4

References:

1. Ayabe, S.-I., Udagawa, A. and Furuya, T. NAD(P)H-dependent 6'-deoxychalcone synthase activity in Glycyrrhiza echinata cells induced by yeast extract. Arch. Biochem. Biophys. 261 (1988) 458-462. [PMID: 3355160]

2. Heller, W. and Hahlbrock, K. Highly purified "flavanone synthase" from parsley catalyzes the formation of naringenin chalcone. Arch. Biochem. Biophys. 200 (1980) 617-619. [PMID: 7436427]

3. Yahyaa, M., Ali, S., Davidovich-Rikanati, R., Ibdah, M., Shachtier, A., Eyal, Y., Lewinsohn, E. and Ibdah, M. Characterization of three chalcone synthase-like genes from apple (Malus x domestica Borkh.). Phytochemistry 140 (2017) 125-133. [PMID: 28482241]

[EC 2.3.1.74 created 1984, modified 2018]

*EC 2.3.1.97

Accepted name: glycylpeptide N-tetradecanoyltransferase

Reaction: tetradecanoyl-CoA + an N-terminal-glycyl-[protein] = CoA + an N-terminal-N-tetradecanoylglycyl-[protein]

Glossary: tetradecanoyl-CoA = myristoyl-CoA

Other name(s): NMT (gene name); peptide N-myristoyltransferase; myristoyl-CoA-protein N-myristoyltransferase; myristoyl-coenzyme A:protein N-myristoyl transferase; myristoylating enzymes; protein N-myristoyltransferase; tetradecanoyl-CoA:glycylpeptide N-tetradecanoyltransferase

Systematic name: tetradecanoyl-CoA:N-terminal-glycine-[protein] N-tetradecanoyltransferase

Comments: The enzyme catalyses the transfer of myristic acid from myristoyl-CoA to the amino group of the N-terminal glycine residue in a variety of eukaryotic proteins. It uses an ordered Bi Bi reaction in which myristoyl-CoA binds to the enzyme prior to the binding of the peptide substrate, and CoA release precedes the release of the myristoylated peptide. The enzyme from yeast is profoundly affected by amino acids further from the N-terminus, and is particularly stimulated by a serine residue at position 5.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 110071-61-9

References:

1. Guertin, D., Gris-Miron, L. and Riendeau, D. Identification of a 51-kilodalton polypeptide fatty acyl chain acceptor in soluble extracts from mouse cardiac tissue. Biochem. Cell Biol. 64 (1986) 1249-1255. [PMID: 3566958]

2. Heuckeroth, R.O., Towler, D.A., Adams, S.P., Glaser, L. and Gordon, J.I. 11-(Ethylthio)undecanoic acid. A myristic acid analogue of altered hydrophobicity which is functional for peptide N-myristoylation with wheat germ and yeast acyltransferase. J. Biol. Chem. 263 (1988) 2127-2133. [PMID: 3123489]

3. Towler, D.A., Adams, S.P., Eubanks, S.R., Towery, D.S., Jackson-Machelski, E., Glaser, L. and Gordon, J.I. Purification and characterization of yeast myristoyl CoA:protein N-myristoyltransferase. Proc. Natl Acad. Sci. USA 84 (1987) 2708-2712. [PMID: 3106975]

4. McIlhinney, R.A., Young, K., Egerton, M., Camble, R., White, A. and Soloviev, M. Characterization of human and rat brain myristoyl-CoA:protein N-myristoyltransferase: evidence for an alternative splice variant of the enzyme. Biochem. J. 333 (1998) 491-495. [PMID: 9677304]

5. Farazi, T.A., Waksman, G. and Gordon, J.I. Structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoylCoA and peptide provide insights about substrate recognition and catalysis. Biochemistry 40 (2001) 6335-6343. [PMID: 11371195]

[EC 2.3.1.97 created 1989, modified 1990, modified 2018]

EC 2.3.1.269

Accepted name: apolipoprotein N-acyltransferase

Reaction: a phosphoglycerolipid + an [apolipoprotein]-S-1,2-diacyl-sn-glyceryl-L-cysteine = a 1-lyso-phosphoglycerolipid + a [lipoprotein]-N-acyl-S-1,2-diacyl-sn-glyceryl-L-cysteine

Other name(s): lnt (gene name); Lnt

Systematic name: phosphoglyceride:[apolipoprotein]-S-1,2-diacyl-sn-glyceryl-L-cysteine N-acyltransferase

Comments: This bacterial enzyme transfers a fatty acid from a membrane phospholipid to form an amide linkage with the N-terminal cysteine residue of apolipoproteins, generating a triacylated molecule.

References:

1. Gupta, S.D. and Wu, H.C. Identification and subcellular localization of apolipoprotein N-acyltransferase in Escherichia coli. FEMS Microbiol. Lett. 62 (1991) 37-41. [PMID: 2032623]

2. Robichon, C., Vidal-Ingigliardi, D. and Pugsley, A.P. Depletion of apolipoprotein N-acyltransferase causes mislocalization of outer membrane lipoproteins in Escherichia coli. J. Biol. Chem. 280 (2005) 974-983. [PMID: 15513925]

3. Hillmann, F., Argentini, M. and Buddelmeijer, N. Kinetics and phospholipid specificity of apolipoprotein N-acyltransferase. J. Biol. Chem. 286 (2011) 27936-27946. [PMID: 21676878]

[EC 2.3.1.269 created 2018]

EC 2.3.1.270

Accepted name: lyso-ornithine lipid O-acyltransferase

Reaction: a lyso-ornithine lipid + an acyl-[acyl-carrier protein] = an ornithine lipid + a holo-[acyl-carrier protein]

Glossary: a lyso-ornithine lipid = an Nα-[(3R)-3-hydroxyacyl]-L-ornithine
an ornithine lipid = an Nα-[(3R)-3-(acyloxy)acyl]-L-ornithine

Other name(s): olsA (gene name)

Systematic name: Nα-[(3R)-hydroxy-acyl]-L-ornithine O-acyltransferase

Comments: This bacterial enzyme catalyses the second step in the formation of ornithine lipids.

References:

1. Weissenmayer, B., Gao, J.L., Lopez-Lara, I.M. and Geiger, O. Identification of a gene required for the biosynthesis of ornithine-derived lipids. Mol. Microbiol. 45 (2002) 721-733. [PMID: 12139618]

2. Aygun-Sunar, S., Bilaloglu, R., Goldfine, H. and Daldal, F. Rhodobacter capsulatus OlsA is a bifunctional enzyme active in both ornithine lipid and phosphatidic acid biosynthesis. J. Bacteriol. 189 (2007) 8564-8574. [PMID: 17921310]

3. Lewenza, S., Falsafi, R., Bains, M., Rohs, P., Stupak, J., Sprott, G.D. and Hancock, R.E. The olsA gene mediates the synthesis of an ornithine lipid in Pseudomonas aeruginosa during growth under phosphate-limiting conditions, but is not involved in antimicrobial peptide susceptibility. FEMS Microbiol. Lett. 320 (2011) 95-102. [PMID: 21535098]

[EC 2.3.1.270 created 2018]

EC 2.3.1.271

Accepted name: L-glutamate-5-semialdehyde N-acetyltransferase

Reaction: acetyl-CoA + L-glutamate-5-semialdehyde = CoA + N-acetyl-L-glutamate 5-semialdehyde

Other name(s): MPR1 (gene name); MPR2 (gene name)

Systematic name: acetyl-CoA:L-glutamate-5-semialdehyde N-acetyltransferase

Comments: The enzyme, characterized from the yeast Saccharomyces cerevisiae Σ1278b, N-acetylates L-glutamate-5-semialdehyde, an L-proline biosynthesis/utilization intermediate, into N-acetyl-L-glutamate 5-semialdehyde, an intermediate of L-arginine biosynthesis, under oxidative stress conditions. Its activity results in conversion of L-proline to L-arginine, and reduction in the concentration of L-glutamate 5-semialdehyde and its equilibrium partner, (S)-1-pyrroline-5-carboxylate, which has been linked to production of reactive oxygen species stress. The enzyme also acts on (S)-1-acetylazetidine-2-carboxylate, a toxic L-proline analog produced by some plants, resulting in its detoxification and conferring resistance on the yeast.

References:

1. Shichiri, M., Hoshikawa, C., Nakamori, S. and Takagi, H. A novel acetyltransferase found in Saccharomyces cerevisiae Σ1278b that detoxifies a proline analogue, azetidine-2-carboxylic acid. J. Biol. Chem. 276 (2001) 41998-42002. [PMID: 11555637]

2. Nomura, M. and Takagi, H. Role of the yeast acetyltransferase Mpr1 in oxidative stress: regulation of oxygen reactive species caused by a toxic proline catabolism intermediate. Proc. Natl Acad. Sci. USA 101 (2004) 12616-12621. [PMID: 15308773]

3. Nishimura, A., Kotani, T., Sasano, Y. and Takagi, H. An antioxidative mechanism mediated by the yeast N-acetyltransferase Mpr1: oxidative stress-induced arginine synthesis and its physiological role. FEMS Yeast Res. 10 (2010) 687-698. [PMID: 20550582]

4. Nishimura, A., Nasuno, R. and Takagi, H. The proline metabolism intermediate Δ1-pyrroline-5-carboxylate directly inhibits the mitochondrial respiration in budding yeast. FEBS Lett. 586 (2012) 2411-2416. [PMID: 22698729]

5. Nasuno, R., Hirano, Y., Itoh, T., Hakoshima, T., Hibi, T. and Takagi, H. Structural and functional analysis of the yeast N-acetyltransferase Mpr1 involved in oxidative stress tolerance via proline metabolism. Proc. Natl Acad. Sci. USA 110 (2013) 11821-11826. [PMID: 23818613]

[EC 2.3.1.271 created 2018]

EC 2.3.1.272

Accepted name: 2-acetylphloroglucinol acetyltransferase

Reaction: 2 2-acetylphloroglucinol = 2,4-diacetylphloroglucinol + phloroglucinol

Glossary: phloroglucinol = benzene-1,3,5-triol

Other name(s): MAPG ATase

Systematic name: 2-acetylphloroglucinol C-acetyltransferase

Comments: The enzyme from the bacterium Pseudomonas sp YGJ3 is composed of three subunits named PhlA, PhlB and PhlC. Production of 2,4-diacetylphloroglucinol, which has antibiotic activity, is strongly inhibited by chloride ions.

References:

1. Hayashi, A., Saitou, H., Mori, T., Matano, I., Sugisaki, H. and Maruyama, K. Molecular and catalytic properties of monoacetylphloroglucinol acetyltransferase from Pseudomonas sp. YGJ3. Biosci. Biotechnol. Biochem. 76 (2012) 559-566. [PMID: 22451400]

[EC 2.3.1.272 created 2018]

[EC 2.4.1.95 Deleted entry: bilirubin-glucuronoside glucuronosyltransferase (EC 2.4.1.95 created 1978, deleted 2018)]

*EC 2.4.1.102

Accepted name: β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,6-N-acetylglucosaminyltransferase

Reaction: UDP-N-acetyl-α-D-glucosamine + O3-[β-D-galactosyl-(1→3)-N-acetyl-α-D-galactosaminyl]-L-seryl/threonyl-[protein] = UDP + O3-{β-D-galactosyl-(1→3)-[N-acetyl-β-D-glucosaminyl-(1→6)]-N-acetyl-α-D-galactosaminyl}-L-seryl/threonyl-[protein]

Glossary: core 1 = O3-[β-D-galactosyl-(1→3)-N-acetyl-α-D-galactosaminyl]-L-seryl/threonyl-[protein]
core 2 = O3-{β-D-galactosyl-(1→3)-[N-acetyl-β-D-glucosaminyl-(1→6)]-N-acetyl-α-D-galactosaminyl}-L-seryl/threonyl-[protein]

Other name(s): O-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase I; β6-N-acetylglucosaminyltransferase; uridine diphosphoacetylglucosamine-mucin β-(1→6)-acetylglucosaminyltransferase; core 2 acetylglucosaminyltransferase; core 6-β-GlcNAc-transferase A; UDP-N-acetyl-D-glucosamine:O-glycosyl-glycoprotein (N-acetyl-D-glucosamine to N-acetyl-D-galactosamine of β-D-galactosyl-1,3-N-acetyl-D-galactosaminyl-R) β-1,6-N-acetyl-D-glucosaminyltransferase; GCNT1; GCNT3; UDP-N-acetyl-D-glucosamine:O-glycosyl-glycoprotein (N-acetyl-D-glucosamine to N-acetyl-D-galactosamine of β-D-galactosyl-(1→3)-N-acetyl-D-galactosaminyl-R) 6-β-N-acetyl-D-glucosaminyltransferase

Systematic name: UDP-N-acetyl-α-D-glucosamine:O3-[β-D-galactosyl-(1→3)-N-acetyl-α-D-galactosaminyl]-glycoprotein 6-β-N-acetyl-D-glucosaminyltransferase (configuration-inverting)

Comments: The enzyme catalyses the addition of N-acetyl-α-D-glucosamine to the core 1 structure of O-glycans forming core 2.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 95978-15-7

References:

1. Brockhausen, I., Rachaman, E.S., Matta, K.L. and Schachter, H. The separation by liquid chromatography (under elevated pressure) of phenyl, benzyl, and O-nitrophenyl glycosides of oligosaccharides. Analysis of substrates and products for four N-acetyl-D-glucosaminyl-transferases involved in mucin synthesis. Carbohydr. Res. 120 (1983) 3-16. [PMID: 6226356]

2. Williams, D., Longmore, G., Matta, K.L. and Schachter, H. Mucin synthesis. II. Substrate specificity and product identification studies on canine submaxillary gland UDP-GlcNAc:Gal β1-3GalNAc(GlcNAc→GalNAc) β6-N-acetylglucosaminyltransferase. J. Biol. Chem. 255 (1980) 11253-11261. [PMID: 6449508]

3. Williams, D. and Schachter, H. Mucin synthesis. I. Detection in canine submaxillary glands of an N-acetylglucosaminyltransferase which acts on mucin substrates. J. Biol. Chem. 255 (1980) 11247-11252. [PMID: 6449507]

[EC 2.4.1.102 created 1983, modified 2018]

*EC 2.4.1.146

Accepted name: β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,3-N-acetylglucosaminyltransferase

Reaction: UDP-N-acetyl-α-D-glucosamine + 3-O-{β-D-galactosyl-(1→3)-[N-acetyl-β-D-glucosaminyl-(1→6)]-N-acetyl-α-D-galactosaminyl}-L-seryl/threonyl-[protein] = UDP + 3-O-{N-acetyl-β-D-glucosaminyl-(1→3)-β-D-galactosyl-(1→3)-[N-acetyl-β-D-glucosaminyl-(1→6)]-N-acetyl-α-D-galactosaminyl}-L-seryl/threonyl-[protein]

Glossary: core 2 = 3-O-{β-D-galactosyl-(1→3)-[N-acetyl-β-D-glucosaminyl-(1→6)]-N-acetyl-α-D-galactosaminyl}-L-seryl/threonyl-[protein]

Other name(s): O-glycosyl-oligosaccharide-glycoprotein N-acetylglucosaminyltransferase II; uridine diphosphoacetylglucosamine-mucin β(1→3)-acetylglucosaminyltransferase (elongating); elongation 3β-GalNAc-transferase; UDP-N-acetyl-D-glucosamine:O-glycosyl-glycoprotein (N-acetyl-D-glucosamine to β-D-galactose of β-D-galactosyl-1,3-(N-acetyl-D-glucosaminyl-1,6)-N-acetyl-D-galactosaminyl-R) β-1,3-N-acetyl-D-glucosaminyltransferase; UDP-N-acetyl-D-glucosamine:β-D-galactosyl-(1→3)-[N-acetyl-D-glucosaminyl-(1→6)]-N-acetyl-D-galactosaminyl-R 3-β-N-acetyl-D-glucosaminyltransferase; B3GNT3 (gene name)

Systematic name: UDP-N-acetyl-α-D-glucosamine:3-O-{β-D-galactosyl-(1→3)-[N-acetyl-β-D-glucosaminyl-(1→6)]-N-acetyl-α-D-galactosaminyl}-L-seryl/threonyl-[protein] 3-β-N-acetyl-D-glucosaminyltransferase (configuration-inverting)

Comments: The enzyme catalyses the addition of N-acetyl-α-D-glucosamine to the core 2 structure of O-glycans.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 87927-99-9

References:

1. Brockhausen, I., Rachaman, E.S., Matta, K.L. and Schachter, H. The separation by liquid chromatography (under elevated pressure) of phenyl, benzyl, and O-nitrophenyl glycosides of oligosaccharides. Analysis of substrates and products for four N-acetyl-D-glucosaminyl-transferases involved in mucin synthesis. Carbohydr. Res. 120 (1983) 3-16. [PMID: 6226356]

2. Shiraishi, N., Natsume, A., Togayachi, A., Endo, T., Akashima, T., Yamada, Y., Imai, N., Nakagawa, S., Koizumi, S., Sekine, S., Narimatsu, H. and Sasaki, K. Identification and characterization of three novel β 1,3-N-acetylglucosaminyltransferases structurally related to the β 1,3-galactosyltransferase family. J. Biol. Chem. 276 (2001) 3498-3507. [PMID: 11042166]

[EC 2.4.1.146 created 1984, modified 2018]

*EC 2.4.1.155

Accepted name: α-1,6-mannosyl-glycoprotein 6-β-N-acetylglucosaminyltransferase

Reaction: UDP-N-acetyl-α-D-glucosamine + β-D-GlcNAc-(1→2)-[β-D-GlcNAc-(1→4)]-α-D-Man-(1→3)-[β-D-GlcNAc-(1→2)-α-D-Man-(1→6)]-β-D-Man-(1→4)-β-D-GlcNAc-(1→4)-β-D-GlcNAc-N-Asn-[protein] = UDP + β-D-GlcNAc-(1→2)-[β-D-GlcNAc-(1→4)]-α-D-Man-(1→3)-[β-D-GlcNAc-(1→2)-[β-D-GlcNAc-(1→6)]-α-D-Man-(1→6)]-β-D-Man-(1→4)-β-D-GlcNAc-(1→4)-β-D-GlcNAc-N-Asn-[protein]

For diagram of reaction click here.

Other name(s): MGAT5 (gene name); N-acetylglucosaminyltransferase V; α-mannoside β-1,6-N-acetylglucosaminyltransferase; uridine diphosphoacetylglucosamine-α-mannoside β1→6-acetylglucosaminyltransferase; UDP-N-acetylglucosamine:α-mannoside-β1,6 N-acetylglucosaminyltransferase; α-1,3(6)-mannosylglycoprotein β-1,6-N-acetylglucosaminyltransferase; GnTV; GlcNAc-T V; UDP-N-acetyl-D-glucosamine:6-[2-(N-acetyl-β-D-glucosaminyl)-α-D-mannosyl]-glycoprotein 6-β-N-acetyl-D-glucosaminyltransferase

Systematic name: UDP-N-acetyl-α-D-glucosamine:N-acetyl-β-D-glucosaminyl-(1→2)-α-D-mannosyl-(1→6)-β-D-mannosyl-glycoprotein 6-β-N-acetyl-D-glucosaminyltransferase (configuration-inverting)

Comments: Requires Mg2+. The enzyme, found in vertebrates, participates in the processing of N-glycans in the Golgi apparatus. It catalyses the addition of N-acetylglucosamine in β 1-6 linkage to the α-linked mannose of biantennary N-linked oligosaccharides, and thus enables the synthesis of tri- and tetra-antennary complexes.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 83588-90-3

References:

1. Cummings, R.D., Trowbridge, I.S. and Kornfeld, S. A mouse lymphoma cell line resistant to the leukoagglutinating lectin from Phaseolus vulgaris is deficient in UDP-GlcNAc: α-D-mannoside β1,6 N-acetylglucosaminyltransferase. J. Biol. Chem. 257 (1982) 13421-13427. [PMID: 6216250]

2. Hindsgaul, O., Tahir, S.H., Srivastava, O.P. and Pierce, M. The trisaccharide β-D-GlcpNAc-(1→2)-α-D-Manp-(1→6)-β-D-Manp, as its 8-methoxycarbonyloctyl glycoside, is an acceptor selective for N-acetylglucosaminyltransferase V. Carbohydr. Res. 173 (1988) 263-272. [PMID: 2834054]

3. Shoreibah, M.G., Hindsgaul, O. and Pierce, M. Purification and characterization of rat kidney UDP-N-acetylglucosamine: α-6-D-mannoside β-1,6-N-acetylglucosaminyltransferase. J. Biol. Chem. 267 (1992) 2920-2927. [PMID: 1531335]

4. Gu, J., Nishikawa, A., Tsuruoka, N., Ohno, M., Yamaguchi, N., Kangawa, K. and Taniguchi, N. Purification and characterization of UDP-N-acetylglucosamine: α-6-D-mannoside β 1-6N-acetylglucosaminyltransferase (N-acetylglucosaminyltransferase V) from a human lung cancer cell line. J. Biochem. 113 (1993) 614-619. [PMID: 8393437]

5. Park, C., Jin, U.H., Lee, Y.C., Cho, T.J. and Kim, C.H. Characterization of UDP-N-acetylglucosamine:α-6-D-mannoside β-1,6-N-acetylglucosaminyltransferase V from a human hepatoma cell line Hep3B. Arch. Biochem. Biophys. 367 (1999) 281-288. [PMID: 10395745]

6. Saito, T., Miyoshi, E., Sasai, K., Nakano, N., Eguchi, H., Honke, K. and Taniguchi, N. A secreted type of β 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation: a novel function of GnT-V distinct from the original glycosyltransferase activity. J. Biol. Chem. 277 (2002) 17002-17008. [PMID: 11872751]

[EC 2.4.1.155 created 1986, modified 2001, modified 2018]

*EC 2.4.1.226

Accepted name: N-acetylgalactosaminyl-proteoglycan 3-β-glucuronosyltransferase

Reaction: (1) UDP-α-D-glucuronate + [protein]-3-O-(β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-serine = UDP + [protein]-3-O-(β-D-GlcA-(1→3)-β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-serine
(2) UDP-α-D-glucuronate + [protein]-3-O-([β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)]n-β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-serine = UDP + [protein]-3-O-(β-D-GlcA-(1→3)-[β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)]n-β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-serine

For diagram of reaction click here.

Other name(s): chondroitin glucuronyltransferase II; α-D-glucuronate:N-acetyl-β-D-galactosaminyl-(1→4)-β-D-glucuronosyl-proteoglycan 3-β-glucuronosyltransferase; UDP-α-D-glucuronate:N-acetyl-β-D-galactosaminyl-(1→4)-β-D-glucuronosyl-proteoglycan 3-β-glucuronosyltransferase

Systematic name: UDP-α-D-glucuronate:[protein]-3-O-(β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-serine = UDP + [protein]-3-O-(β-D-GlcA-(1→3)-β-D-GalNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-serine 3-β-glucuronosyltransferase (configuration-inverting)

Comments: Involved in the biosynthesis of chondroitin and dermatan sulfate. The human chondroitin synthetase is a bifunctional glycosyltransferase, which has the 3-β-glucuronosyltransferase and 4-β-N-acetylgalactosaminyltransferase (EC 2.4.1.175) activities required for the synthesis of the chondroitin sulfate disaccharide repeats. Similar chondroitin synthase ’co-polymerases’ can be found in Pasteurella multocida and Escherichia coli. There is also another human protein with apparently only the 3-β-glucuronosyltransferase activity.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 269077-98-7

References:

1. Kitagawa, H., Uyama, T. and Sugahara, K. Molecular cloning and expression of a human chondroitin synthase. J. Biol. Chem. 276 (2001) 38721-38726. [PMID: 11514575]

2. DeAngelis, P.L. and Padgett-McCue, A.J. Identification and molecular cloning of a chondroitin synthase from Pasteurella multocida type F. J. Biol. Chem. 275 (2000) 24124-24129. [PMID: 10818104]

3. Ninomiya, T., Sugiura, N., Tawada, A., Sugimoto, K., Watanabe, H. and Kimata, K. Molecular cloning and characterization of chondroitin polymerase from Escherichia coli strain K4. J. Biol. Chem. 277 (2002) 21567-21575. [PMID: 11943778]

4. Gotoh, M., Yada, T., Sato, T., Akashima, T., Iwasaki, H., Mochizuki, H., Inaba, N., Togayachi, A., Kudo, T., Watanabe, H., Kimata, K. and Narimatsu, H. Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase which transfers glucuronic acid to N-acetylgalactosamine. J. Biol. Chem. 277 (2002) 38179-38188. [PMID: 12145278]

[EC 2.4.1.226 created 2002, modified 2018]

EC 2.4.1.356

Accepted name: glucosyl-dolichyl phosphate glucuronosyltransferase

Reaction: UDP-α-D-glucuronate + an archaeal dolichyl β-D-glucosyl phosphate = UDP + an archaeal dolichyl β-D-glucuronosyl-(1→3)-β-D-glucosyl phosphate

Other name(s): aglG (gene name)

Systematic name: UDP-α-D-glucuronate:dolichyl phosphate glucuronosyltransferase (configuration-inverting)

Comments: The enzyme, characterized from the halophilic archaeon Haloferax volcanii, participates in the protein N-glycosylation pathway. Dolichol used by archaea is different from that used by eukaryotes. It is much shorter (C55-C60) and is α,ω-saturated. However, in vitro the enzyme was also able to act on a substrate with an unsaturated end.

References:

1. Yurist-Doutsch, S., Abu-Qarn, M., Battaglia, F., Morris, H.R., Hitchen, P.G., Dell, A. and Eichler, J. aglF, aglG and aglI, novel members of a gene island involved in the N-glycosylation of the Haloferax volcanii S-layer glycoprotein. Mol. Microbiol. 69 (2008) 1234-1245. [PMID: 18631242]

2. Elharar, Y., Podilapu, A.R., Guan, Z., Kulkarni, S.S. and Eichler, J. Assembling glycan-charged dolichol phosphates: chemoenzymatic synthesis of a Haloferax volcanii N-glycosylation pathway intermediate. Bioconjug Chem 28 (2017) 2461-2470. [PMID: 28809486]

[EC 2.4.1.356 created 2018]

EC 2.4.1.357

Accepted name: phlorizin synthase

Reaction: UDP-α-D-glucose + phloretin = UDP + phlorizin

For diagram of reaction click here.

Glossary: phloretin = 3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)propan-1-one
phlorizin = 3-(4-hydroxyphenyl)-1-[2-(β-D-glucopyranosyloxy)-4,6-dihydroxyphenyl]propan-1-one

Other name(s): MdPGT1: P2’GT

Systematic name: UDP-α-D-glucose:phloretin 2'-O-D-glucosyltransferase

Comments: Isolated from Malus X domestica (apple). Phlorizin inhibits sodium-linked glucose transporters. It gives the characteristic flavour of apples and cider.

References:

1. Jugdé, H., Nguy, D., Moller, I., Cooney, J.M. and Atkinson, R.G. Isolation and characterization of a novel glycosyltransferase that converts phloretin to phlorizin, a potent antioxidant in apple. FEBS J. 275 (2008) 3804-3814. [PMID: 18573104]

2. Yahyaa, M., Davidovich-Rikanati, R., Eyal, Y., Sheachter, A., Marzouk, S., Lewinsohn, E. and Ibdah, M. Identification and characterization of UDP-glucose:Phloretin 4'-O-glycosyltransferase from Malus x domestica Borkh. Phytochemistry 130 (2016) 47-55. [PMID: 27316677]

[EC 2.4.1.357 created 2018]

EC 2.5.1.144

Accepted name: S-sulfo-L-cysteine synthase (O-acetyl-L-serine-dependent)

Reaction: O-acetyl-L-serine + thiosulfate = S-sulfo-L-cysteine + acetate

For diagram of reaction click here.

Glossary: O-acetyl-L-serine = (2S)-3-acetyloxy-2-aminopropanoic acid

Other name(s): cysteine synthase B; cysM (gene name); CS26 (gene name)

Systematic name: O-acetyl-L-serine:thiosulfate 2-amino-2-carboxyethyltransferase

Comments: In plants, the activity is catalysed by a chloroplastic enzyme that plays an important role in chloroplast function and is essential for light-dependent redox regulation within the chloroplast. The bacterial enzyme also catalyses the activity of EC 2.5.1.47, cysteine synthase. cf. EC 2.8.5.1, S-sulfo-L-cysteine synthase (3-phospho-L-serine-dependent).

References:

1. Hensel, G. and Truper, H.G. O-Acetylserine sulfhydrylase and S-sulfocysteine synthase activities of Rhodospirillum tenue. Arch. Microbiol. 134 (1983) 227-232. [PMID: 6615127]

2. Nakamura, T., Iwahashi, H. and Eguchi, Y. Enzymatic proof for the identity of the S-sulfocysteine synthase and cysteine synthase B of Salmonella typhimurium. J. Bacteriol. 158 (1984) 1122-1127. [PMID: 6373737]

3. Bermudez, M.A., Paez-Ochoa, M.A., Gotor, C. and Romero, L.C. Arabidopsis S-sulfocysteine synthase activity is essential for chloroplast function and long-day light-dependent redox control. Plant Cell 22 (2010) 403-416. [PMID: 20179139]

4. Bermudez, M.A., Galmes, J., Moreno, I., Mullineaux, P.M., Gotor, C. and Romero, L.C. Photosynthetic adaptation to length of day is dependent on S-sulfocysteine synthase activity in the thylakoid lumen. Plant Physiol. 160 (2012) 274-288. [PMID: 22829322]

5. Gotor, C. and Romero, L.C. S-sulfocysteine synthase function in sensing chloroplast redox status. Plant Signal Behav 8 (2013) e23313. [PMID: 23333972]

[EC 2.5.1.144 created 2018]

EC 2.5.1.145

Accepted name: phosphatidylglycerol—prolipoprotein diacylglyceryl transferase

Reaction: L-1-phosphatidyl-sn-glycerol + a [prolipoprotein]-L-cysteine = sn-glycerol 1-phosphate + an [prolipoprotein]-S-1,2-diacyl-sn-glyceryl-L-cysteine

Other name(s): lgt (gene name)

Systematic name: L-1-phosphatidyl-sn-glycerol:[prolipoprotein]-L-cysteine diacyl-sn-glyceryltransferase

Comments: This bacterial enzyme, which is associated with the membrane, catalyses the transfer of an sn-1,2-diacylglyceryl group from phosphatidylglycerol to the sulfhydryl group of the prospective N-terminal cysteine of a prolipoprotein, the first step in the formation of mature triacylated lipoproteins.

References:

1. Sankaran, K. and Wu, H.C. Lipid modification of bacterial prolipoprotein. Transfer of diacylglyceryl moiety from phosphatidylglycerol. J. Biol. Chem. 269 (1994) 19701-19706. [PMID: 8051048]

2. Qi, H.Y., Sankaran, K., Gan, K. and Wu, H.C. Structure-function relationship of bacterial prolipoprotein diacylglyceryl transferase: functionally significant conserved regions. J. Bacteriol. 177 (1995) 6820-6824. [PMID: 7592473]

3. Gan, K., Sankaran, K., Williams, M.G., Aldea, M., Rudd, K.E., Kushner, S.R. and Wu, H.C. The umpA gene of Escherichia coli encodes phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (lgt) and regulates thymidylate synthase levels through translational coupling. J. Bacteriol. 177 (1995) 1879-1882. [PMID: 7896715]

4. Sankaran, K., Gan, K., Rash, B., Qi, H.Y., Wu, H.C. and Rick, P.D. Roles of histidine-103 and tyrosine-235 in the function of the prolipoprotein diacylglyceryl transferase of Escherichia coli. J. Bacteriol. 179 (1997) 2944-2948. [PMID: 9139912]

5. Pailler, J., Aucher, W., Pires, M. and Buddelmeijer, N. Phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt) of Escherichia coli has seven transmembrane segments, and its essential residues are embedded in the membrane. J. Bacteriol. 194 (2012) 2142-2151. [PMID: 22287519]

[EC 2.5.1.145 created 2018]

EC 2.5.1.146

Accepted name: 3-geranyl-3-[(Z)-2-isocyanoethenyl]indole synthase

Reaction: geranyl diphosphate + 3-[(Z)-2-isocyanoethenyl]-1H-indole = 3-geranyl-3-[(Z)-2-isocyanoethenyl]-1H-indole + diphosphate

Other name(s): famD2 (gene name)

Systematic name: geranyl-diphosphate:3-[(Z)-2-isocyanoethenyl]-1H-indole geranyltransferase

Comments: The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, participates in the biosynthesis of hapalindole-type alkaloids.

References:

1. Li, S., Lowell, A.N., Yu, F., Raveh, A., Newmister, S.A., Bair, N., Schaub, J.M., Williams, R.M. and Sherman, D.H. Hapalindole/ambiguine biogenesis Is mediated by a Cope rearrangement, C-C bond-forming cascade. J. Am. Chem. Soc. 137 (2015) 15366-15369. [PMID: 26629885]

[EC 2.5.1.146 created 2018]

*EC 2.6.1.92

Accepted name: UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine transaminase

Reaction: UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine + 2-oxoglutarate = UDP-2-acetamido-2,6-dideoxy-β-L-arabino-hex-4-ulose + L-glutamate

Other name(s): PseC; UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine:2-oxoglutarate aminotransferase; UDP-β-L-threo-pentapyranos-4-ulose transaminase; UDP-4-dehydro-6-deoxy-D-glucose transaminase

Systematic name: UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine:2-oxoglutarate transaminase

Comments: A pyridoxal 5'-phosphate protein. The enzyme transfers the primary amino group of L-glutamate to C-4'' of UDP-4-dehydro sugars, forming a C-N bond in a stereo configuration opposite to that of UDP. The enzyme from the bacterium Bacillus cereus has been shown to act on UDP-2-acetamido-2,6-dideoxy-β-L-arabino-hex-4-ulose, UDP-β-L-threo-pentapyranos-4-ulose, UDP-4-dehydro-6-deoxy-D-glucose, and UDP-2-acetamido-2,6-dideoxy-α-D-xylo-hex-4-ulose. cf. EC 2.6.1.34, UDP-N-acetylbacillosamine transaminase, which catalyses a similar reaction, but forms the C-N bond in the same stereo configuration as that of UDP.

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

References:

1. Schoenhofen, I.C., McNally, D.J., Vinogradov, E., Whitfield, D., Young, N.M., Dick, S., Wakarchuk, W.W., Brisson, J.R. and Logan, S.M. Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways. J. Biol. Chem. 281 (2006) 723-732. [PMID: 16286454]

2. Schoenhofen, I.C., Lunin, V.V., Julien, J.P., Li, Y., Ajamian, E., Matte, A., Cygler, M., Brisson, J.R., Aubry, A., Logan, S.M., Bhatia, S., Wakarchuk, W.W. and Young, N.M. Structural and functional characterization of PseC, an aminotransferase involved in the biosynthesis of pseudaminic acid, an essential flagellar modification in Helicobacter pylori. J. Biol. Chem. 281 (2006) 8907-8916. [PMID: 16421095]

3. Mostafavi, A.Z. and Troutman, J.M. Biosynthetic assembly of the Bacteroides fragilis capsular polysaccharide A precursor bactoprenyl diphosphate-linked acetamido-4-amino-6-deoxygalactopyranose. Biochemistry 52 (2013) 1939-1949. [PMID: 23458065]

4. Hwang, S., Li, Z., Bar-Peled, Y., Aronov, A., Ericson, J. and Bar-Peled, M. The biosynthesis of UDP-D-FucNAc-4N-(2)-oxoglutarate (UDP-Yelosamine) in Bacillus cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp protein that ligates 2-oxoglutarate to UDP-4-amino-sugars. J. Biol. Chem 289 (2014) 35620-35632. [PMID: 25368324]

[EC 2.6.1.92 created 2011, modified 2018]

EC 2.7.7.100

Accepted name: SAMP-activating enzyme

Reaction: ATP + [SAMP]-Gly-Gly = diphosphate + [SAMP]-Gly-Gly-AMP

Glossary: SAMP = small archaeal modifier protein = ubiquitin-like small archaeal modifier protein

Other name(s): UbaA (ambiguous); SAMP-activating enzyme E1 (ambiguous)

Systematic name: ATP:SAMP adenylyltransferase

Comments: Contains Zn2+. The enzyme catalyses the activation of SAMPs (Small Archaeal Modifier Proteins), which are ubiquitin-like proteins found only in the Archaea, by catalysing the ATP-dependent formation of a SAMP adenylate in which the C-terminal glycine of SAMP is bound to AMP via an acyl-phosphate linkage. The product of this activity can accept a sulfur atom to form a thiocarboxylate moiety that acts as a sulfur carrier involved in thiolation of tRNA and other metabolites such as molybdopterin. Alternatively, the enzyme can also catalyse the transfer of SAMP from its activated form to an internal cysteine residue, leading to a process termed SAMPylation (see EC 6.2.1.55, E1 SAMP-activating enzyme).

References:

1. Miranda, H.V., Nembhard, N., Su, D., Hepowit, N., Krause, D.J., Pritz, J.R., Phillips, C., Soll, D. and Maupin-Furlow, J.A. E1- and ubiquitin-like proteins provide a direct link between protein conjugation and sulfur transfer in archaea. Proc. Natl Acad. Sci. USA 108 (2011) 4417-4422. [PMID: 21368171]

2. Maupin-Furlow, J.A. Ubiquitin-like proteins and their roles in archaea. Trends Microbiol 21 (2013) 31-38. [PMID: 23140889]

3. Hepowit, N.L., de Vera, I.M., Cao, S., Fu, X., Wu, Y., Uthandi, S., Chavarria, N.E., Englert, M., Su, D., Sll, D., Kojetin, D.J. and Maupin-Furlow, J.A. Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea. FEBS J. 283 (2016) 3567-3586. [PMID: 27459543]

[EC 2.7.7.100 created 2018]

EC 2.8.5 Thiosulfotransferases

EC 2.8.5.1

Accepted name: S-sulfo-L-cysteine synthase (3-phospho-L-serine-dependent)

Reaction: 3-phospho-L-serine + thiosulfate = S-sulfo-L-cysteine + phosphate

Other name(s): cysK2 (gene name)

Systematic name: thiosulfate:3-phospho-L-serine thiosulfotransferase

Comments: The enzyme, which has been characterized from the bacterium Mycobacterium tuberculosis, has no activity with O-acetyl-L-serine. Requires pyridoxal 5'-phosphate. cf. EC 2.5.1.144, S-sulfo-L-cysteine synthase (O-acetyl-L-serine-dependent).

References:

1. Steiner, E.M., Both, D., Lossl, P., Vilaplana, F., Schnell, R. and Schneider, G. CysK2 from Mycobacterium tuberculosis is an O-phospho-L-serine-dependent S-sulfocysteine synthase. J. Bacteriol. 196 (2014) 3410-3420. [PMID: 25022854]

[EC 2.8.5.1 created 2018]

EC 3.1.6.20

Accepted name: S-sulfosulfanyl-L-cysteine sulfohydrolase

Reaction: (1) [SoxY protein]-S-sulfosulfanyl-L-cysteine + H2O = [SoxY protein]-S-sulfanyl-L-cysteine + sulfate
(2) [SoxY protein]-S-(2-sulfodisulfanyl)-L-cysteine + H2O = [SoxY protein]-S-disulfanyl-L-cysteine + sulfate

Other name(s): SoxB

Systematic name: [SoxY protein]-S-sulfosulfanyl-L-cysteine sulfohydrolase

Comments: Contains Mn2+. The enzyme is part of the Sox enzyme system, which participates in a bacterial thiosulfate oxidation pathway that produces sulfate. It catalyses two reactions in the pathway. In both cases the enzyme hydrolyses a sulfonate moiety that is bound (either directly or via a sulfane) to a cysteine residue of a SoxY protein, releasing sulfate. The enzyme from Paracoccus pantotrophus contains a pyroglutamate (cycloglutamate) at its N-terminus.

References:

1. Quentmeier, A. and Friedrich, C.G. The cysteine residue of the SoxY protein as the active site of protein-bound sulfur oxidation of Paracoccus pantotrophus GB17. FEBS Lett. 503 (2001) 168-172. [PMID: 11513876]

2. Friedrich, C.G., Rother, D., Bardischewsky, F., Quentmeier, A. and Fischer, J. Oxidation of reduced inorganic sulfur compounds by bacteria: emergence of a common mechanism. Appl. Environ. Microbiol. 67 (2001) 2873-2882. [PMID: 11425697]

3. Quentmeier, A., Hellwig, P., Bardischewsky, F., Grelle, G., Kraft, R. and Friedrich, C.G. Sulfur oxidation in Paracoccus pantotrophus: interaction of the sulfur-binding protein SoxYZ with the dimanganese SoxB protein. Biochem. Biophys. Res. Commun. 312 (2003) 1011-1018. [PMID: 14651972]

4. Epel, B., Schafer, K.O., Quentmeier, A., Friedrich, C. and Lubitz, W. Multifrequency EPR analysis of the dimanganese cluster of the putative sulfate thiohydrolase SoxB of Paracoccus pantotrophus. J. Biol. Inorg. Chem. 10 (2005) 636-642. [PMID: 16133204]

5. Hensen, D., Sperling, D., Truper, H.G., Brune, D.C. and Dahl, C. Thiosulphate oxidation in the phototrophic sulphur bacterium Allochromatium vinosum. Mol. Microbiol. 62 (2006) 794-810. [PMID: 16995898]

6. Grabarczyk, D.B. and Berks, B.C. Intermediates in the Sox sulfur oxidation pathway are bound to a sulfane conjugate of the carrier protein SoxYZ. PLoS One 12 (2017) e0173395. [PMID: 28257465]

[EC 3.1.6.20 created 2018]

*EC 3.2.1.170

Accepted name: mannosylglycerate hydrolase

Reaction: 2-O-(α-D-mannopyranosyl)-D-glycerate + H2O = D-mannopyranose + D-glycerate

Other name(s): MgH

Systematic name: 2-O-(α-D-mannopyranosyl)-D-glycerate D-mannohydrolase

Comments: The enzyme occurs in thermophilic bacteria and has been characterized in Thermus thermophilus and Rubrobacter radiotolerans. It also has been identified in the moss Selaginella moellendorffii.

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

References:

1. Alarico, S., Empadinhas, N. and da Costa, M.S. A new bacterial hydrolase specific for the compatible solutes α-D-mannopyranosyl-(1→2)-D-glycerate and α-D-glucopyranosyl-(1→2)-D-glycerate. Enzyme Microb. Technol. 52 (2013) 77-83. [PMID: 23273275]

2. Nobre, A., Empadinhas, N., Nobre, M.F., Lourenco, E.C., Maycock, C., Ventura, M.R., Mingote, A. and da Costa, M.S. The plant Selaginella moellendorffii possesses enzymes for synthesis and hydrolysis of the compatible solutes mannosylglycerate and glucosylglycerate. Planta 237 (2013) 891-901. [PMID: 23179444]

[EC 3.2.1.170 created 2011, modified 2018]

*EC 3.3.1.2

Accepted name: S-adenosyl-L-methionine hydrolase (L-homoserine-forming)

Reaction: S-adenosyl-L-methionine + H2O = L-homoserine + S-methyl-5'-thioadenosine

Glossary: S-methyl-L-methionine sulfonium salt = (S)-3-amino-3-carboxypropyldi(methyl)sulfonium salt

Other name(s): S-adenosylmethionine cleaving enzyme; methylmethionine-sulfonium-salt hydrolase; adenosylmethionine lyase; adenosylmethionine hydrolase; S-adenosylmethionine hydrolase; S-adenosyl-L-methionine hydrolase

Systematic name: S-adenosyl-L-methionine hydrolase (L-homoserine-forming)

Comments: Also hydrolyses S-methyl-L-methionine to dimethyl sulfide and homoserine. cf. EC 3.13.1.8, S-adenosyl-L-methionine hydrolase (adenosine-forming).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37288-62-3

References:

1. Mazelis, M., Levin, B. and Mallinson, N. Decomposition of methyl methionine sulfonium salts by a bacterial enzyme. Biochim. Biophys. Acta 105 (1965) 106-114. [PMID: 5849106]

[EC 3.3.1.2 created 1972, modified 1976, modified 2018]

EC 3.13.1.8

Accepted name: S-adenosyl-L-methionine hydrolase (adenosine-forming)

Reaction: S-adenosyl-L-methionine + H2O = adenosine + L-methionine

Other name(s): SAM hydroxide adenosyltransferase

Systematic name: S-adenosyl-L-methionine hydrolase (adenosine-forming)

Comments: The enzyme, found in bacteria and archaea, catalyses a nucleophilic attack of water at the C5' carbon of S-adenosyl-L-methionine to generate adenosine and L-methionine. May be involved in regulating SAM levels in the cell. cf. EC 3.3.1.2, S-adenosyl-L-methionine hydrolase (L-homoserine-forming)

References:

1. Eustaquio, A.S., Harle, J., Noel, J.P. and Moore, B.S. S-Adenosyl-L-methionine hydrolase (adenosine-forming), a conserved bacterial and archaeal protein related to SAM-dependent halogenases. Chembiochem 9 (2008) 2215-2219. [PMID: 18720493]

2. Deng, H., McMahon, S.A., Eustaquio, A.S., Moore, B.S., Naismith, J.H. and O'Hagan, D. Mechanistic insights into water activation in SAM hydroxide adenosyltransferase (duf-62). Chembiochem 10 (2009) 2455-2459. [PMID: 19739191]

[EC 3.13.1.8 created 2018]

EC 4.1.1.110

Accepted name: bisphosphomevalonate decarboxylase

Reaction: (R)-3,5-bisphosphomevalonate = isopentenyl phosphate + CO2 + phosphate

Other name(s): mevalonate 3,5-bisphosphate decarboxylase

Systematic name: (R)-3,5-bisphosphomevalonate carboxy-lyase (isopentenyl-phosphate-forming)

Comments: The enzyme participates in an alternative mevalonate pathway that takes place in extreme acidophiles of the Thermoplasmatales order. cf. EC 4.1.1.99, phosphomevalonate decarboxylase.

References:

1. Vinokur, J.M., Cummins, M.C., Korman, T.P. and Bowie, J.U. An adaptation to life in acid through a novel mevalonate pathway. Sci Rep 6 (2016) 39737. [PMID: 28004831]

[EC 4.1.1.110 created 2018]

EC 4.1.1.111

Accepted name: siroheme decarboxylase

Reaction: siroheme = 12,18-didecarboxysiroheme + 2 CO2

For diagram of reaction click here.

Other name(s): sirohaem decarboxylase; nirDLHG (gene name); ahbABC (gene name)

Systematic name: siroheme carboxy-lyase

Comments: The enzyme from archaea is involved in an alternative heme biosynthesis pathway. The enzyme from denitrifying bacteria is involved in the heme d1 biosynthesis pathway.

References:

1. Bali, S., Lawrence, A.D., Lobo, S.A., Saraiva, L.M., Golding, B.T., Palmer, D.J., Howard, M.J., Ferguson, S.J. and Warren, M.J. Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Proc. Natl Acad. Sci. USA 108 (2011) 18260-18265. [PMID: 21969545]

2. Kuhner, M., Haufschildt, K., Neumann, A., Storbeck, S., Streif, J. and Layer, G. The alternative route to heme in the methanogenic archaeon Methanosarcina barkeri. Archaea 2014 (2014) 327637. [PMID: 24669201]

3. Palmer, D.J., Schroeder, S., Lawrence, A.D., Deery, E., Lobo, S.A., Saraiva, L.M., McLean, K.J., Munro, A.W., Ferguson, S.J., Pickersgill, R.W., Brown, D.G. and Warren, M.J. The structure, function and properties of sirohaem decarboxylase--an enzyme with structural homology to a transcription factor family that is part of the alternative haem biosynthesis pathway. Mol. Microbiol. 93 (2014) 247-261. [PMID: 24865947]

4. Haufschildt, K., Schmelz, S., Kriegler, T.M., Neumann, A., Streif, J., Arai, H., Heinz, D.W. and Layer, G. The crystal structure of siroheme decarboxylase in complex with iron-uroporphyrin III reveals two essential histidine residues. J. Mol. Biol. 426 (2014) 3272-3286. [PMID: 25083922]

[EC 4.1.1.111 created 2018]

EC 4.4.1.37

Accepted name: pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase

Reaction: (1) [LarE]-L-cysteine + pyridin-1-ium-3,5-dicarboxylate mononucleotide + ATP = [LarE]-dehydroalanine + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + AMP + diphosphate (overall reaction)
(1a) ATP + pyridin-1-ium-3,5-dicarboxylate mononucleotide = diphosphate + 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate
(1b) 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate + [LarE]-L-cysteine = AMP + [LarE]-S-[5-carboxy-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl]-L-cysteine
(1c) [LarE]-S-[5-carboxy-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl]-L-cysteine = [LarE]-dehydroalanine + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide
(2) [LarE]-L-cysteine + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + ATP = [LarE]-dehydroalanine + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide + AMP + diphosphate (overall reaction)
(2a) ATP + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide = diphosphate + 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate
(2b) 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate + [LarE]-L-cysteine = AMP + [LarE]-S-[1-(5-O-phosphono-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl]-L-cysteine
(2c) [LarE]-S-[1-(5-O-phosphono-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl]-L-cysteine = [LarE]-dehydroalanine + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide

Other name(s): LarE; P2CMN sulfurtransferase; pyridinium-3,5-biscarboxylic acid mononucleotide sulfurtransferase; P2TMN synthase

Systematic name: [LarE]-S-[1-(5-O-phosphono-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl]-L-cysteine pyridin-1-ium-3,5-dicarbothioate-mononucleotide-lyase (ATP-consuming)

Comments: This enzyme, found in Lactobacillus plantarum, is involved in the biosynthesis of a nickel-pincer cofactor. The process starts when one enzyme molecule adenylates pyridinium-3,5-dicarboxylate mononucleotide (P2CMN) and covalently binds the adenylated product to an intrinsic cysteine residue. Next, the enzyme cleaves the carbon-sulfur bond, liberating pyridinium-3-carboxylate-5-thiocarboxylate mononucleotide (PCTMN) and leaving a 2-aminoprop-2-enoate (dehydroalanine) residue attached to the protein. Since the cysteine residue is not regenerated in vivo, the enzyme is inactivated during the process. A second enzyme molecule then repeats the process with PCTMN, adenylating it and covalently binding it to the same cysteine residue, followed by liberation of pyridinium-3,5-bisthiocarboxylate mononucleotide (P2TMN) and the inactivation of the second enzyme molecule.

References:

1. Desguin, B., Goffin, P., Viaene, E., Kleerebezem, M., Martin-Diaconescu, V., Maroney, M.J., Declercq, J.P., Soumillion, P. and Hols, P. Lactate racemase is a nickel-dependent enzyme activated by a widespread maturation system. Nat Commun 5 (2014) 3615. [PMID: 24710389]

2. Desguin, B., Soumillion, P., Hols, P. and Hausinger, R.P. Nickel-pincer cofactor biosynthesis involves LarB-catalyzed pyridinium carboxylation and LarE-dependent sacrificial sulfur insertion. Proc. Natl Acad. Sci. USA 113 (2016) 5598-5603. [PMID: 27114550]

3. Fellner, M., Desguin, B., Hausinger, R.P. and Hu, J. Structural insights into the catalytic mechanism of a sacrificial sulfur insertase of the N-type ATP pyrophosphatase family, LarE. Proc. Natl Acad. Sci. USA 114 (2017) 9074-9079. [PMID: 28784764]

[EC 4.4.1.37 created 2018]

EC 6.2.1.55

Accepted name: E1 SAMP-activating enzyme

Reaction: ATP + [SAMP]-Gly-Gly + [E1 SAMP-activating enzyme]-L-cysteine = S-[[SAMP]-Gly-Gly]-[[E1 SAMP-activating enzyme]-L-cysteine] + AMP + diphosphate (overall reaction)
(1a) ATP + [SAMP]-Gly-Gly = diphosphate + [SAMP]-Gly-Gly-AMP
(1b) [SAMP]-Gly-Gly-AMP + [E1 SAMP-activating enzyme]-L-cysteine = S-[[SAMP]-Gly-Gly]-[[E1 SAMP-activating enzyme]-L-cysteine] + AMP

Glossary: SAMP = small archaeal modifier protein = ubiquitin-like small archaeal modifier protein

Other name(s): UbaA; SAMP-activating enzyme E1

Systematic name: [SAMP]:[E1 SAMP-activating enzyme] ligase (AMP-forming)

Comments: Contains Zn2+. The enzyme catalyses the activation of SAMPs (Small Archaeal Modifier Proteins), which are ubiquitin-like proteins found only in the Archaea. SAMPs are involved in protein degradation, and also act as sulfur carriers involved in thiolation of tRNA and other metabolites such as molybdopterin. The enzyme catalyses the ATP-dependent formation of a SAMP adenylate intermediate in which the C-terminal glycine of SAMP is bound to AMP via an acyl-phosphate linkage (reaction 1). This intermediate can accept a sulfur atom to form a thiocarboxylate moiety in a mechanism that is not yet understood. Alternatively, the E1 enzyme can transfer SAMP from its activated form to an internal cysteine residue, releasing AMP (reaction 2). In this case SAMP is subsequently transferred to a lysine residue in a target protein in a process termed SAMPylation. Auto-SAMPylation (attachment of SAMP to lysine residues within the E1 enzyme) has been observed. cf. EC 2.7.7.100, SAMP-activating enzyme.

References:

1. Miranda, H.V., Nembhard, N., Su, D., Hepowit, N., Krause, D.J., Pritz, J.R., Phillips, C., Soll, D. and Maupin-Furlow, J.A. E1- and ubiquitin-like proteins provide a direct link between protein conjugation and sulfur transfer in archaea. Proc. Natl Acad. Sci. USA 108 (2011) 4417-4422. [PMID: 21368171]

2. Maupin-Furlow, J.A. Ubiquitin-like proteins and their roles in archaea. Trends Microbiol 21 (2013) 31-38. [PMID: 23140889]

3. Miranda, H.V., Antelmann, H., Hepowit, N., Chavarria, N.E., Krause, D.J., Pritz, J.R., Basell, K., Becher, D., Humbard, M.A., Brocchieri, L. and Maupin-Furlow, J.A. Archaeal ubiquitin-like SAMP3 is isopeptide-linked to proteins via a UbaA-dependent mechanism. Mol. Cell. Proteomics 13 (2014) 220-239. [PMID: 24097257]

4. Hepowit, N.L., de Vera, I.M., Cao, S., Fu, X., Wu, Y., Uthandi, S., Chavarria, N.E., Englert, M., Su, D., Sll, D., Kojetin, D.J. and Maupin-Furlow, J.A. Mechanistic insight into protein modification and sulfur mobilization activities of noncanonical E1 and associated ubiquitin-like proteins of Archaea. FEBS J. 283 (2016) 3567-3586. [PMID: 27459543]

[EC 6.2.1.55 created 2018]


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