EC 1.13.12 to EC 1.14.12

EC 1.13 Acting on single donors with incorporation of molecular oxygen (oxygenases) [continued]
EC 1.13.12 With incorporation of one atom of oxygen (internal monooxygenases or internal mixed function oxidases)
EC 1.13.99 Miscellaneous

EC 1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
EC 1.14.11 With 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
EC 1.14.12 With NADH or NADPH as one donor, and incorporation of two atoms of oxygen into one donor
EC 1.14.13 With NADH or NADPH as one donor, and incorporation of one atom of oxygen
EC 1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
EC 1.14.15 With reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
EC 1.14.16 With reduced pteridine as one donor, and incorporation of one atom of oxygen
EC 1.14.17 With reduced ascorbate as one donor, and incorporation of one atom of oxygen
EC 1.14.18 With another compound as one donor, and incorporation of one atom of oxygen
EC 1.14.19 With oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water
EC 1.14.20 With 2-oxoglutarate as one donor, and the other dehydrogenated
EC 1.14.21 With NADH or NADPH as one donor, and the other dehydrogenated

EC 1.14.99 Miscellaneous

Contents

Accepted name: arginine 2-monooxygenase

Reaction: L-arginine + O₂ = 4-guanidinobutanamide + CO₂ + H₂O

Other name(s): arginine monooxygenase; arginine decarboxylase; arginine oxygenase (decarboxylating); arginine decarboxy-oxidase

Systematic name: L-arginine:oxygen 2-oxidoreductase (decarboxylating)

Comments: A flavoprotein. Also acts on canavanine and homoarginine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9027-36-5

References:

1. Olomucki, A., Pho, D.B., Lebar, R., Delcambe, L. and Thoai, N.V. Arginine oxygénase décarboxylante. V. Purification et nature flavinique. Biochim. Biophys. Acta 151 (1968) 353-366. [PMID: 4295160]

2. Thoai, N.V. and Olomucki, A. Arginine décarboxy-oxydase. I. Caract&egrav;res et nature de l'enzyme. Biochim. Biophys. Acta 59 (1962) 533-544.

3. Thoai, N.V. and Olomucki, A. Arginine décarboxy-oxydase. II. Oxydation de la canavanine et de l'homoarginine en β-guanidopropionamide et en δ-guanidovaleramide. Biochim. Biophys. Acta 59 (1962) 545-552.

EC 1.13.12.2

Accepted name: lysine 2-monooxygenase

Reaction: L-lysine + O₂ = 5-aminopentanamide + CO₂ + H₂O

Other name(s): lysine oxygenase; lysine monooxygenase; L-lysine-2-monooxygenase

Systematic name: L-lysine:oxygen 2-oxidoreductase (decarboxylating)

Comments: A flavoprotein (FAD). Also acts on other diamino acids.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9031-22-5

References:

1. Nakazawa, T., Hori, K. and Hayaishi, O. Studies on monooxygenases. V. Manifestation of amino acid oxidase activity by L-lysine monooxygenase. J. Biol. Chem. 247 (1972) 3439-3444. [PMID: 4624115]

2. Takeda, H. and Hayaishi, O. Crystalline L-lysine oxygenase. J. Biol. Chem. 241 (1966) 2733-2736. [PMID: 5911646]

3. Takeda, H., Yamamoto, S., Kojima, Y. and Hayaishi, O. Studies on monooxygenases. I. General properties of crystalline L-lysine monooxygenase. J. Biol. Chem. 244 (1969) 2935-2941. [PMID: 5772467]

EC 1.13.12.3

Accepted name: tryptophan 2-monooxygenase

Reaction: L-tryptophan + O₂ = (indol-3-yl)acetamide + CO₂ + H₂O

Other name(s): tms1 (gene name); iaaM (gene name)

Systematic name: L-tryptophan:oxygen 2-oxidoreductase (decarboxylating)

Comments: The enzyme, studied from phytopathogenic bacteria such as Pseudomonas savastanoi, is involved in a pathway for the production of (indol-3-yl)acetate (IAA), the main auxin hormone in plants.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37256-65-8

References:

1. Kosuge, T., Heskett, M.G. and Wilson, E.E. Microbial synthesis and degradation of indole-3-acetic acid. I. The conversion of L-tryptophan to indole-3-acetamide by an enzyme system from Pseudomonas savastanoi. J. Biol. Chem. 241 (1966) 3738-3744. [PMID: 5916389]

2. Kuo, T.T. and Kosuge, T. Factors influencing the production and further metabolism of indole-3-acetic acid by Pseudomonas savastanoi. J. Gen. Appl. Microbiol. 15 (1969) 51-63.

3. Hutcheson, S.W. and Kosuge, T. Regulation of 3-indoleacetic acid production in Pseudomonas syringae pv. savastanoi. Purification and properties of tryptophan 2-monooxygenase. J. Biol. Chem. 260 (1985) 6281-6287. [PMID: 3997822]

4. Onckelen, H.V., Prinsen, E., Inze, D., Ruedeisheim, P., Lijsebettens, M.V., Follin, A., Schell, J., Montagu, M.V. and Greef, J.D. AgrobacteriumT-DNA gene1codes for tryptophan 2-monooxygenase activity in tobacco crown gall cells. FEBS Lett. 198 (1986) 357-360.

5. Emanuele, J.J. and Fitzpatrick, P.F. Mechanistic studies of the flavoprotein tryptophan 2-monooxygenase. 1. Kinetic mechanism. Biochemistry 34 (1995) 3710-3715. [PMID: 7893667]

EC 1.13.12.4

Accepted name: lactate 2-monooxygenase

Reaction: (S)-lactate + O₂ = acetate + CO₂ + H₂O

Other name(s): lactate oxidative decarboxylase; lactate oxidase; lactic oxygenase; lactate oxygenase; lactic oxidase; L-lactate monooxygenase; lactate monooxygenase; L-lactate-2-monooxygenase

Systematic name: (S)-lactate:oxygen 2-oxidoreductase (decarboxylating)

Comments: A flavoprotein (FMN). Formerly EC 1.1.3.2.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9028-72-2

References:

1. Hayaishi, O. and Sutton, W.B. Enzymatic oxygen fixation into acetate concomitant with the enzymatic decarboxylation of L-lactate. J. Am. Chem. Soc. 79 (1957) 4809-4810..

2. Sutton, W.B. Mechanism of action and crystalization of lactic oxidative decarboxylase from Mycobacterium phlei. J. Biol. Chem. 226 (1957) 395-405.

EC 1.13.12.5

Accepted name: Renilla-type luciferase

Reaction: coelenterazine h + O₂ = excited coelenteramide h monoanion + CO₂ (over-all reaction)
(1a) coelenterazine h + O₂ = coelenterazine h dioxetanone
(1b) coelenterazine h dioxetanone = excited coelenteramide h monoanion + CO₂

For diagram of reaction, click here

Glossary: coelenterazine h = Renilla luciferin = 2,8-dibenzyl-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one
coelenteramide h = Renilla oxyluciferin = N-[3-benzyl-5-(4-hydroxyphenyl)pyrazin-2-yl]-2-phenylacetamide

Other name(s): Renilla-luciferin 2-monooxygenase; luciferase (Renilla luciferin); Renilla-luciferin:oxygen 2-oxidoreductase (decarboxylating)

Systematic name: coelenterazine h:oxygen 2-oxidoreductase (decarboxylating)

Comments: This enzyme has been studied from the soft coral Renilla reniformis. Before the reaction occurs the substrate is sequestered by a coelenterazine-binding protein. Elevation in the concentration of calcium ions releases the substrate, which then interacts with the luciferase. Upon binding the substrate, the enzyme catalyses an oxygenation, producing a very short-lived hydroperoxide that cyclizes into a dioxetanone structure, which collapses, releasing a CO₂ molecule. The spontaneous breakdown of the dioxetanone releases the energy (about 50 kcal/mole) that is necessary to generate the excited state of the coelenteramide product, which is the singlet form of the monoanion. In vivo the product undergoes the process of nonradiative energy transfer to an accessory protein, a green fluorescent protein (GFP), which results in green bioluminescence. In vitro, in the absence of GFP, the product emits blue light.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 61869-41-8

References:

1. Cormier, M.J., Hori, K. and Anderson, J.M. Bioluminescence in coelenterates. Biochim. Biophys. Acta 346 (1974) 137-164. [PMID: 4154104]

2. Hori, K., Anderson, J.M., Ward, W.W. and Cormier, M.J. Renilla luciferin as the substrate for calcium induced photoprotein bioluminescence. Assignment of luciferin tautomers in aequorin and mnemiopsin. Biochemistry 14 (1975) 2371-2376. [PMID: 237531]

3. Anderson, J.M., Charbonneau, H. and Cormier, M.J. Mechanism of calcium induction of Renilla bioluminescence. Involvement of a calcium-triggered luciferin binding protein. Biochemistry 13 (1974) 1195-1200. [PMID: 4149963]

4. Shimomura, O. and Johnson, F.H. Chemical nature of bioluminescence systems in coelenterates. Proc. Natl. Acad. Sci. USA 72 (1975) 1546-1549. [PMID: 236561]

5. Charbonneau, H. and Cormier, M.J. Ca²⁺-induced bioluminescence in Renilla reniformis. Purification and characterization of a calcium-triggered luciferin-binding protein. J. Biol. Chem. 254 (1979) 769-780. [PMID: 33174]

6. Lorenz, W.W., McCann, R.O., Longiaru, M. and Cormier, M.J. Isolation and expression of a cDNA encoding Renilla reniformis luciferase. Proc. Natl. Acad. Sci. USA 88 (1991) 4438-4442. [PMID: 1674607]

7. Loening, A.M., Fenn, T.D. and Gambhir, S.S. Crystal structures of the luciferase and green fluorescent protein from Renilla reniformis. J. Mol. Biol. 374 (2007) 1017-1028. [PMID: 17980388]

EC 1.13.12.6

Accepted name: Cypridina-luciferin 2-monooxygenase

Reaction: Cypridina luciferin + O₂ = oxidized Cypridina luciferin + CO₂ + hν

For diagram click here.

Glossary: Cypridina-luciferin = (3-{3,7-dihydro-6-(1H-indol-3-yl)-2-[(S)-1-methylpropyl]-3-oxoimidazo[1,2-a]pyrazin-8-yl}propyl)guanidine

Other name(s): Cypridina-type luciferase; luciferase (Cypridina luciferin); Cypridina luciferase

Systematic name: Cypridina-luciferin:oxygen 2-oxidoreductase (decarboxylating)

Comments: Cypridina is a bioluminescent crustacea. The luciferins (and presumably the luciferases, since they cross-react) of some luminous fish (e.g. Apogon, Parapriacanthus, Porichthys) are apparently similar. The enzyme may be assayed by measurement of light emission.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 61969-99-1

References:

1. Cormier, M.J., Crane, J.M.,Jr. and Nakano, Y Evidence for the identity of the luminescent systems of Porichthys porosissimus (fish) and Cypridina hilgendorfii (crustacean). Biochem. Biophys. Res. Commun. 29 (1967) 747-752. [PMID: 5624784]

2. Karpetsky, T.P. and White, E.H. The synthesis of Cypridina etioluciferamine and the proof of the structure of Cypridina luciferin. Tetrahedron 29 (1973) 3761-3773.

3. Kishi, Y., Goto, T., Hirata, Y., Shiromura, O. and Johnson, F.H. Cypridina bioluminescence. I. Structure of Cypridina luciferin. Tetrahedron Lett. (1966) 3427-3436.

4. Tsuji, F.I., Lynch, R.V. and Stevens, C.L. Some properties of luciferase from the bioluminescent crustacean, Cypridina hilgendorfii. Biochemistry 13 (1974) 5204-5209. [PMID: 4433517]

EC 1.13.12.7

Accepted name: firefly luciferase

Reaction: D-firefly luciferin + O₂ + ATP = firefly oxyluciferin + CO₂ + AMP + diphosphate + hν

For diagram of reaction, click here

Glossary: D-firefly luciferin = Photinus-luciferin = (S)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate
firefly oxyluciferin = 4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazol-4-one

Other name(s): Photinus-luciferin 4-monooxygenase (ATP-hydrolysing); luciferase (firefly luciferin); Photinus luciferin 4-monooxygenase (adenosine triphosphate-hydrolyzing); firefly luciferin luciferase; Photinus pyralis luciferase; Photinus-luciferin:oxygen 4-oxidoreductase (decarboxylating, ATP-hydrolysing)

Systematic name: D-firefly luciferin:oxygen 4-oxidoreductase (decarboxylating, ATP-hydrolysing)

Comments: The enzyme, which is found in fireflies (Lampyridae), is responsible for their biolouminescence. The reaction begins with the formation of an acid anhydride between the carboxylic group of D-firefly luciferin and AMP, with the release of diphosphate. An oxygenation follows, with release of the AMP group and formation of a very short-lived peroxide that cyclizes into a dioxetanone structure, which collapses, releasing a CO₂ molecule. The spontaneous breakdown of the dioxetanone (rather than the hydrolysis of the adenylate) releases the energy (about 50 kcal/mole) that is necessary to generate the excited state of oxyluciferin. The excited luciferin then emitts a photon, returning to its ground state. The enzyme has a secondary acyl-CoA ligase activity when acting on L-firefly luciferin (see EC 6.2.1.52).

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 61970-00-1

References:

1. Green, A. A. and McElroy, W. D. Crystalline firefly luciferase. Biochim. Biophys. Acta 20 (1956) 170-176. [PMID: 13315363]

2. White, E.H., McCapra, F., Field, G.F. and McElroy, W.D. The structure and synthesis of firefly luciferin. J. Am. Chem. Soc. 83 (1961) 2402-2403.

3. Hopkins, T.A., Seliger, H.H., White, E.H. and Cass, M.W. The chemiluminescence of firefly luciferin. A model for the bioluminescent reaction and identification of the product excited state. J. Am. Chem. Soc. 89 (1967) 7148-7150. [PMID: 6064360]

4. White, E.H., Rapaport, E., Hopkins, T.A. and Seliger, H.H. Chemi- and bioluminescence of firefly luciferin. J. Am. Chem. Soc. 91 (1969) 2178-2180. [PMID: 5784183]

5. Koo, J.A., Schmidt, S.P. and Schuster, G.B. Bioluminescence of the firefly: key steps in the formation of the electronically excited state for model systems. Proc. Natl Acad. Sci. USA 75 (1978) 30-33. [PMID: 272645]

6. de Wet, J.R., Wood, K.V., Helinski, D.R. and DeLuca, M. Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia coli. Proc. Natl Acad. Sci. USA 82 (1985) 7870-7873. [PMID: 3906652]

7. Nakamura, M., Maki, S., Amano, Y., Ohkita, Y., Niwa, K., Hirano, T., Ohmiya, Y. and Niwa, H. Firefly luciferase exhibits bimodal action depending on the luciferin chirality. Biochem. Biophys. Res. Commun. 331 (2005) 471-475. [PMID: 15850783]

8. Sundlov, J.A., Fontaine, D.M., Southworth, T.L., Branchini, B.R. and Gulick, A.M. Crystal structure of firefly luciferase in a second catalytic conformation supports a domain alternation mechanism. Biochemistry 51 (2012) 6493-6495. [PMID: 22852753]

EC 1.13.12.8

Accepted name: Watasenia-luciferin 2-monooxygenase

Reaction: Watasenia luciferin + O₂ = oxidized Watasenia luciferin + CO₂ + hν

For diagram click here.

Glossary: Watasenia-luciferin = 8-benzyl-6-(4-sulfooxyphenyl)-2-(4-sulfooxybenzyl)imidazo[1,2-a]pyrazin-3(7H)-one

Other name(s): Watasenia-type luciferase

Systematic name: Watasenia-luciferin:oxygen 2-oxidoreductase (decarboxylating)

Comments: The enzyme from the luminous squid Watasenia may be assayed by measurement of light emission.

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

References:

1. Inoue, S., Kakoi, H. and Goto, T. Squid bioluminescence. III. Isolation and structure of Watasenia luciferin. Tetrahedron Lett. (1976) 2971-2974.

EC 1.13.12.9

Accepted name: phenylalanine 2-monooxygenase

Reaction: L-phenylalanine + O₂ = 2-phenylacetamide + CO₂ + H₂O

Other name(s): L-phenylalanine oxidase (deaminating and decarboxylating); phenylalanine (deaminating, decarboxylating)oxidase

Systematic name: L-phenylalanine:oxygen 2-oxidoreductase (decarboxylating)

Comments: The reaction shown above is about 80% of the reaction catalysed; the remaining 20% is:

    L-phenylalanine + O₂ + H₂O = 3-phenylpyruvic acid + ammonia + H₂O₂

a reaction similar to that of EC 1.4.3.2, L-amino-acid oxidase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 190396-37-3

References:

1. Koyama, H. Purification and characterization of a novel L-phenylalanine oxidase (deaminating and decarboxylating) from Pseudomonas sp. P-501. J. Biochem. (Tokyo) 92 (1982) 1235-1240. [PMID: 7174643]

2. Koyama, H. Oxidation and oxygenation of L-amino acids catalyzed by a L-phenylalanine oxidase (deaminating and decarboxylating) from Pseudomonas sp. P-501. J. Biochem. (Tokyo) 96 (1984) 421-427. [PMID: 6501250]

3. Koyama, H. A simple and rapid enzymatic determination of L-phenylalanine with a novel L-phenylalanine oxidase (deaminating and decarboxylating) from Pseudomonas sp. P-501. Clin. Chim. Acta 1361 (1984) 131-136. [PMID: 6692570]

4. Koyama, H. and Suzuki, H. Spectral and kinetic studies on Pseudomonas L-phenylalanine oxidase (deaminating and decarboxylating). J. Biochem. (Tokyo) 100 (1986) 859-866. [PMID: 3818566]

[EC 1.13.12.10 Deleted entry: lysine 6-monooxygenase. reaction covered by EC 1.14.13.59, L-lysine 6-monooxygenase (NADPH) (EC 1.13.12.10 created 1989, modified 1999, deleted 2001)]

[EC 1.13.12.11 Deleted entry: methylphenyltetrahydropyridine N-monooxygenase. The activity is due to EC 1.14.13.8, flavin-containing monooxygenase. (EC 1.13.12.11 created 1992, deleted 2006)]

[EC 1.13.12.12 Transferred entry: apo-β-carotenoid-14',13'-dioxygenase. The enzyme was misclassified and has been transferred to EC 1.13.11.67, 8-apo-β-carotenoid 14',13'-cleaving dioxygenase (EC 1.13.12.12 created 2000, modified 2001, deleted 2012)]

EC 1.13.12.13

Accepted name: Oplophorus-luciferin 2-monooxygenase

Reaction: Oplophorus luciferin + O₂ = oxidized Oplophorus luciferin + CO₂ + hν

For diagram click here.

Glossary: Oplophorus luciferin = 8-benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one

Other name(s): Oplophorus luciferase

Systematic name: Oplophorus-luciferin:oxygen 2-oxidoreductase (decarboxylating)

Comments: The luciferase from the deep sea shrimp Oplophorus gracilirostris is a complex composed of more than one protein. The enzyme's specificity is quite broad, with both coelenterazine and bisdeoxycoelenterazine being good substrates.

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

References:

1. Shimomura, O., Masugi, T., Johnson, F.H. and Haneda, Y. Properties and reaction mechanism of the bioluminescence system of the deep-sea shrimp Oplophorus gracilorostris. Biochemistry 17 (1978) 994-998. [PMID: 629957]

2. Inouye, S., Watanabe, K., Nakamura, H., Shimomura, O. Secretional luciferase of the luminous shrimp Oplophorus gracilirostris: cDNA cloning of a novel imidazopyrazinone luciferase. FEBS Lett. 481 (2000) 19-25. [PMID: 10984608]

[EC 1.13.12.14 Transferred entry: chlorophyllide-a oxygenase. Now EC 1.14.13.122, chlorophyllide-a oxygenase (EC 1.13.12.14 created 2006, deleted 2011)]

EC 1.13.12.15

Accepted name: 3,4-dihydroxyphenylalanine oxidative deaminase

Reaction: 2 L-dopa + O₂ = 2 3,4-dihydroxyphenylpyruvate + 2 NH₃

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

Other name(s): 3,4-dihydroxy-L-phenylalanine: oxidative deaminase; oxidative deaminase; DOPA oxidative deaminase; DOPAODA

Systematic name: 3,4-dihydroxy-L-phenylalanine:oxygen oxidoreductase (deaminating)

Comments: This enzyme is one of the three enzymes involved in L-dopa (3,4-dihydroxyphenylalanine) catabolism in the non-oxygenic phototrophic bacterium Rubrivivax benzoatilyticus OU5 (and not Rhodobacter sphaeroides OU5 as had been thought [1]), the other two being EC 4.3.1.22 (dihydroxyphenylalanine reductive deaminase) and EC 2.6.1.49 (3,4-dihydroxyphenylalanine transaminase). In addition to L-dopa, the enzyme can also use L-tyrosine, L-phenylalanine, L-tryptophan and glutamate as substrate, but more slowly. The enzyme is inhibited by NADH and 2-oxoglutarate.

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

References:

1. Ranjith, N.K., Ramana, Ch.V. and Sasikala, Ch. Purification and characterization of 3,4-dihydroxyphenylalanine oxidative deaminase from Rhodobacter sphaeroides OU5. Can. J. Microbiol. 54 (2008) 829-834.

EC 1.13.12.16

Accepted name: nitronate monooxygenase

Reaction: ethylnitronate + O₂ = acetaldehyde + nitrite + other products

Other name(s): NMO; 2-nitropropane dioxygenase (incorrect)

Systematic name: nitronate:oxygen 2-oxidoreductase (nitrite-forming)

Comments: Previously classified as 2-nitropropane dioxygenase (EC 1.13.11.32), but it is now recognized that this was the result of the slow ionization of nitroalkanes to their nitronate (anionic) forms. The enzymes from the fungus Neurospora crassa and the yeast Williopsis saturnus var. mrakii (formerly classified as Hansenula mrakii) contain non-covalently bound FMN as the cofactor. Neither hydrogen peroxide nor superoxide were detected during enzyme turnover. Active towards linear alkyl nitronates of lengths between 2 and 6 carbon atoms and, with lower activity, towards propyl-2-nitronate. The enzyme from N. crassa can also utilize neutral nitroalkanes, but with lower activity.

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

References:

1. Francis, K., Russell, B. and Gadda, G. Involvement of a flavosemiquinone in the enzymatic oxidation of nitroalkanes catalyzed by 2-nitropropane dioxygenase. J. Biol. Chem. 280 (2005) 5195-5204. [PMID: 15582992]

2. Ha, J.Y., Min, J.Y., Lee, S.K., Kim, H.S., Kim do, J., Kim, K.H., Lee, H.H., Kim, H.K., Yoon, H.J. and Suh, S.W. Crystal structure of 2-nitropropane dioxygenase complexed with FMN and substrate. Identification of the catalytic base. J. Biol. Chem. 281 (2006) 18660-18667. [PMID: 16682407]

3. Gadda, G. and Francis, K. Nitronate monooxygenase, a model for anionic flavin semiquinone intermediates in oxidative catalysis. Arch. Biochem. Biophys. 493 (2010) 53-61. [PMID: 19577534]

4. Francis, K. and Gadda, G. Kinetic evidence for an anion binding pocket in the active site of nitronate monooxygenase. Bioorg. Chem. 37 (2009) 167-172. [PMID: 19683782]

EC 1.13.12.17

Accepted name: dichloroarcyriaflavin A synthase

Reaction: dichlorochromopyrrolate + 4 O₂ + 4 NADH + 4 H⁺ = dichloroarcyriaflavin A + 2 CO₂ + 6 H₂O + 4 NAD⁺

For diagram of reaction click here

Glossary: dichloro-arcyriaflavin A = rebeccamycin aglycone

Systematic name: dichlorochromopyrrolate,NADH:oxygen 2,5-oxidoreductase (dichloroarcyriaflavin A-forming)

Comments: The conversion of dichlorochromopyrrolate to dichloroarcyriaflavin A is a complex process that involves two enzyme components. RebP is an NAD-dependent cytochrome P₄₅₀ oxygenase that performs an aryl-aryl bond formation yielding the six-ring indolocarbazole scaffold [1]. Along with RebC, a flavin-dependent hydroxylase, it also catalyses the oxidative decarboxylation of both carboxyl groups. The presence of RebC ensures that the only product is the rebeccamycin aglycone dichloroarcyriaflavin A [2]. The enzymes are similar, but not identical, to StaP and StaC, which are involved in the synthesis of staurosporine [3].

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

References:

1. Makino, M., Sugimoto, H., Shiro, Y., Asamizu, S., Onaka, H. and Nagano, S. Crystal structures and catalytic mechanism of cytochrome P₄₅₀ StaP that produces the indolocarbazole skeleton. Proc. Natl. Acad. Sci. USA 104:1159 (2007). [PMID: 17606921]

2. Howard-Jones, A.R. and Walsh, C.T. Staurosporine and rebeccamycin aglycones are assembled by the oxidative action of StaP, StaC, and RebC on chromopyrrolic acid. J. Am. Chem. Soc. 128:1228 (2006). [PMID: 16967980]

3. Sanchez, C., Zhu, L., Brana, A.F., Salas, A.P., Rohr, J., Mendez, C. and Salas, J.A. Combinatorial biosynthesis of antitumor indolocarbazole compounds. Proc. Natl. Acad. Sci. USA 102:461 (2005). [PMID: 15625109]

EC 1.13.12.18

Accepted name: dinoflagellate luciferase

Reaction: dinoflagellate luciferin + O₂ = oxidized dinoflagellate luciferin + H₂O + hν

For diagram of reaction, click here

Glossary: dinoflagellate luciferin = (1S,2S,3S)-1-carboxy-3-(2-carboxyethyl)-12-ethyl-2,8,13,18-tetramethyl-17-vinyl-1,2,3,21-tetrahydro-5,7-ethanobilene-a-19(16H),5²-dione

Other name(s): (dinoflagellate luciferin) luciferase; Gonyaulax luciferase

Systematic name: dinoflagellate-luciferin:oxygen 13²-oxidoreductase

Comments: A luciferase from dinoflagellates such as Gonyaulax polyedra, Lingulodinium polyedrum, Noctiluca scintillans, and Pyrocystis lunula. It is a single protein with three luciferase domains. The luciferin is strongly bound by a luciferin binding protein above a pH of 7.

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

References:

1. Dunlap, J.C. and Hastings, J.W. The biological clock in Gonyaulax controls luciferase activity by regulating turnover. J. Biol. Chem. 256 (1981) 10509-10518. [PMID: 7197271]

2. Morse, D., Pappenheimer, A.M., Jr. and Hastings, J.W. Role of a luciferin-binding protein in the circadian bioluminescent reaction of Gonyaulax polyedra. J. Biol. Chem. 264 (1989) 11822-11826. [PMID: 2745419]

3. Bae, Y.M. and Hastings, J.W. Cloning, sequencing and expression of dinoflagellate luciferase DNA from a marine alga, Gonyaulax polyedra. Biochim. Biophys. Acta 1219 (1994) 449-456. [PMID: 7918642]

4. Li, L. Gonyaulax luciferase: gene structure, protein expression, and purification from recombinant sources. Methods Enzymol. 305 (2000) 249-258. [PMID: 10812605]

5. Morse, D. and Mittag, M. Dinoflagellate luciferin-binding protein. Methods Enzymol. 305 (2000) 258-276. [PMID: 10812606]

6. Schultz, L.W., Liu, L., Cegielski, M. and Hastings, J.W. Crystal structure of a pH-regulated luciferase catalyzing the bioluminescent oxidation of an open tetrapyrrole. Proc. Natl. Acad. Sci. USA 102 (2005) 1378-1383. [PMID: 15665092]

EC 1.13.12.19

Accepted name: 2-oxuglutarate dioxygenase (ethene-forming)

Reaction: 2-oxoglutarate + O₂ = ethene + 3 CO₂ + H₂O

Glossary: ethene = ethylene

Other name(s): ethylene-forming enzyme; EFE; 2-oxoglutarate dioxygenase (ethylene-forming); 2-oxoglutarate:oxygen oxidoreductase (decarboxylating, ethylene-forming)

Systematic name: 2-oxuglutarate:oxygen oxidoreductase (decarboxylating, ethene-forming)

Comments: This is one of two simultaneous reactions catalysed by the enzyme, which is responsible for ethylene production in bacteria of the Pseudomonas syringae group. In the other reaction [EC 1.14.20.7, 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming)] the enzyme catalyses the mono-oxygenation of both 2-oxoglutarate and L-arginine, forming succinate, carbon dioxide and L-hydroxyarginine, which is subsequently cleaved into guanidine and (S)-1-pyrroline-5-carboxylate. The enzymes catalyse two cycles of the ethylene-forming reaction for each cycle of the succinate-forming reaction, so that the stoichiometry of the products ethylene and succinate is 2:1.

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

References:

1. Nagahama, K., Ogawa, T., Fujii, T., Tazaki, M., Tanase, S., Morino, Y. and Fukuda, H. Purification and properties of an ethylene-forming enzyme from Pseudomonas syringae pv. phaseolicola PK2. J. Gen. Microbiol. 137 (1991) 2281-2286. [PMID: 1770346]

2. Fukuda, H., Ogawa, T., Tazaki, M., Nagahama, K., Fujii, T., Tanase, S. and Morino, Y. Two reactions are simultaneously catalyzed by a single enzyme: the arginine-dependent simultaneous formation of two products, ethylene and succinate, from 2-oxoglutarate by an enzyme from Pseudomonas syringae. Biochem. Biophys. Res. Commun. 188 (1992) 483-489. [PMID: 1445291]

3. Fukuda, H., Ogawa, T., Ishihara, K., Fujii, T., Nagahama, K., Omata, T., Inoue, Y., Tanase, S. and Morino, Y. Molecular cloning in Escherichia coli, expression, and nucleotide sequence of the gene for the ethylene-forming enzyme of Pseudomonas syringae pv. phaseolicola PK2. Biochem. Biophys. Res. Commun. 188 (1992) 826-832. [PMID: 1445325]

EC 1.13.12.20

Accepted name: noranthrone monooxygenase

Reaction: norsolorinic acid anthrone + O₂ = norsolorinic acid + H₂O

For diagram of reaction click here.

Glossary: norsolorinic acid anthrone = noranthrone = 2-hexanoyl-1,3,6,8-tetrahydroxyanthracen-9(10H)-one
norsolorinate = 2-hexanoyl-1,3,6,8-tetrahydroxy-9,10-anthraquinone

Other name(s): norsolorinate anthrone oxidase

Systematic name: norsolorinic acid anthrone:oxygen 9-oxidoreductase (norsolorinic acid-forming)

Comments: Involved in the synthesis of aflatoxins in the fungus Aspergillus parasiticus.

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

References:

1. Ehrlich, K.C., Li, P., Scharfenstein, L. and Chang, P.K. HypC, the anthrone oxidase involved in aflatoxin biosynthesis. Appl. Environ. Microbiol. 76 (2010) 3374-3377. [PMID: 20348292]

EC 1.13.12.21

Accepted name: tetracenomycin-F1 monooxygenase

Reaction: tetracenomycin F1 + O₂ = tetracenomycin D3 + H₂O

For diagram of reaction click here.

Glossary: tetracenomycin D3 = 3,8,10,12-tetrahydroxy-1-methyl-6,11-dioxo-6,11-dihydrotetracene-2-carboxylate = 6,11-dihydro-3,8,10,12-tetrahydroxy-1-methyl-6,11-dioxonaphthacene-2-carboxylic acid
tetracenomycin F1 = 3,8,10,12-tetrahydroxy-1-methyl-11-oxo-6,11-dihydro-2-tetracenecarboxylate = 6,11-dihydro-3,8,10,12-tetrahydroxy-1-methyl-11-oxonaphthacene-2-carboxylic acid

Other name(s): tcmH (gene name)

Systematic name: tetracenomycin-F1:oxygen C5-monooxygenase

Comments: The enzyme is involved in biosynthesis of the anthracycline antibiotic tetracenomycin C by the bacterium Streptomyces glaucescens.

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

References:

1. Shen, B. and Hutchinson, C.R. Tetracenomycin F1 monooxygenase: oxidation of a naphthacenone to a naphthacenequinone in the biosynthesis of tetracenomycin C in Streptomyces glaucescens. Biochemistry 32 (1993) 6656-6663. [PMID: 8329392]

EC 1.13.12.22

Accepted name: deoxynogalonate monooxygenase

Reaction: deoxynogalonate + O₂ = nogalonate + H₂O

For diagram of reaction click here.

Glossary: deoxynogalonate = [4,5-dihydroxy-10-oxo-3-(3-oxobutanoyl)-9,10-dihydroanthracen-2-yl]acetate
nogalonate = [4,5-dihydroxy-9,10-dioxo-3-(3-oxobutanoyl)-9,10-dihydroanthracen-2-yl]acetate

Other name(s): SnoaB (gene name); 12-deoxynogalonic acid oxidoreductase; [4,5-dihydroxy-10-oxo-3-(3-oxobutanoyl)-9,10-dihydroanthracen-2-yl]acetate oxidase; [4,5-dihydroxy-10-oxo-3-(3-oxobutanoyl)-9,10-dihydroanthracen-2-yl]acetate monooxygenase; deoxynogalonate oxidoreductase

Systematic name: deoxynogalonate:oxygen oxidoreductase

Comments: The enzyme, characterized from the bacterium Streptomyces nogalater, is involved in the biosynthesis of the aromatic polyketide nogalamycin.

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

References:

1. Koskiniemi, H., Grocholski, T., Schneider, G. and Niemi, J. Expression, purification and crystallization of the cofactor-independent monooxygenase SnoaB from the nogalamycin biosynthetic pathway. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 65 (2009) 256-259. [PMID: 19255477]

2. Grocholski, T., Koskiniemi, H., Lindqvist, Y., Mantsala, P., Niemi, J. and Schneider, G. Crystal structure of the cofactor-independent monooxygenase SnoaB from Streptomyces nogalater: implications for the reaction mechanism. Biochemistry 49 (2010) 934-944. [PMID: 20052967]

EC 1.13.12.23

Accepted name: 4-hydroxy-3-prenylbenzoate synthase

Reaction: 4-hydroxy-3-prenylmandelate + O₂ = 4-hydroxy-3-prenylbenzoate + CO₂ + H₂O

For diagram of reaction, click here

Other name(s): CloR; novR (gene name)

Systematic name: 4-hydroxy-3-prenylmandelate:oxygen oxidoreductase (4-hydroxy-3-prenylbenzoate forming)

Comments: Isolated from the bacterium Streptomyces roseochromogenes DS 12976. A bifunctional enzyme involved in clorobiocin biosynthesis that also catalyses the activity of EC 1.13.11.83, 4-hydroxy-3-prenylphenylpyruvate oxygenase.

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

References:

1. Pojer, F., Kahlich, R., Kammerer, B., Li, S.M. and Heide, L. CloR, a bifunctional non-heme iron oxygenase involved in clorobiocin biosynthesis. J. Biol. Chem. 278 (2003) 30661-30668. [PMID: 12777382]

EC 1.13.12.24

Accepted name: calcium-regulated photoprotein

Reaction: [apoaequorin] + coelenterazine + O₂ + 3 Ca²⁺ = [excited state blue fluorescent protein] + CO₂ (overall reaction)
(1a) [apoaequorin] + coelenterazine = [apoaequorin containing coelenterazine]
(1b) [apoaequorin containing coelenterazine] + O₂ = [aequorin]
(1c) [aequorin] + 3 Ca²⁺ = [aequorin] 1,2-dioxetan-3-one
(1d) [aequorin] 1,2-dioxetan-3-one = [excited state blue fluorescent protein] + CO₂

Glossary: coelenterazine = 8-benzyl-2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)imidazo[1,2-a]pyrazin-3(7H)-one
coelenteramide = N-[3-benzyl-5-(4-hydroxyphenyl)pyrazin-2-yl]-2-(4-hydroxyphenyl)acetamide
aequorin = the non-covalent complex formed by apoaequorin polypeptide and coelenterazine-2-hydroperoxide.
blue fluorescent protein = the non-covalent complex formed by Ca²⁺-bound apoaequorin polypeptide and coelenteramide

Other name(s): Ca²⁺-regulated photoprotein; calcium-activated photoprotein; aequorin; obelin; halistaurin; mitrocomin; phialidin; clytin; mnemiopsin; berovin

Systematic name: coelenterazine:oxygen 2-oxidoreductase (decarboxylating, calcium-dependent)

Comments: Ca²⁺-regulated photoproteins are found in a variety of bioluminescent marine organisms, mostly coelenterates, and are responsible for their light emission. The best studied enzyme is from the jellyfish Aequorea victoria. The enzyme tightly binds the imidazolopyrazinone derivative coelenterazine, which is then peroxidized by oxygen. The hydroperoxide is stably bound until three Ca²⁺ ions bind to the protein, inducing a structural change that results in the formation of a 1,2-dioxetan-3-one ring, followed by decarboxylation and generation of a protein-bound coelenteramide in an excited state. The calcium-bound protein-product complex is known as a blue fluorescent protein. In vivo the energy is transferred to a green fluorescent protein (GFP) by Fšrster resonance energy transfer. In vitro, in the absence of GFP, coelenteramide emits a photon of blue light while returning to its ground state.

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

References:

1. Shimomura, O., Johnson, F. H., and Saiga, Y. Purification and properties of aequorin, a bio-(chemi-) luminescent protein from the jellyfish, Aequorea aequorea. Fed. Proc. 21 (1962) 401.

2. Morise, H., Shimomura, O., Johnson, F.H. and Winant, J. Intermolecular energy transfer in the bioluminescent system of Aequorea. Biochemistry 13 (1974) 2656-2662. [PMID: 4151620]

3. Inouye, S., Noguchi, M., Sakaki, Y., Takagi, Y., Miyata, T., Iwanaga, S., Miyata, T. and Tsuji, F.I. Cloning and sequence analysis of cDNA for the luminescent protein aequorin. Proc. Natl Acad. Sci. USA 82 (1985) 3154-3158. [PMID: 3858813]

4. Head, J.F., Inouye, S., Teranishi, K. and Shimomura, O. The crystal structure of the photoprotein aequorin at 2.3 Å resolution. Nature 405 (2000) 372-376. [PMID: 10830969]

5. Deng, L., Vysotski, E.S., Markova, S.V., Liu, Z.J., Lee, J., Rose, J. and Wang, B.C. All three Ca²⁺-binding loops of photoproteins bind calcium ions: the crystal structures of calcium-loaded apo-aequorin and apo-obelin. Protein Sci. 14 (2005) 663-675. [PMID: 15689515]

Contents

Accepted name: inositol oxygenase

Reaction: myo-inositol + O₂ = D-glucuronate + H₂O

For diagram click here.

Other name(s): meso-inositol oxygenase; myo-inositol oxygenase; MOO

Systematic name: myo-inositol:oxygen oxidoreductase

Comments: An iron protein. Formerly EC 1.13.1.11 and EC 1.99.2.6.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9029-59-8

References:

1. Charalampous, F.C. Biochemical studies on inositol. V. Purification and properties of the enzyme that cleaves inositol to D-glucuronic acid. J. Biol. Chem. 234 (1959) 220-227.

2. Reddy, C.C., Swan, J.S. and Hamilton, G.A. myo-Inositol oxygenase from hog kidney. I. Purification and characterization of the oxygenase and of an enzyme complex containing the oxygenase and D-glucuronate reductase. J. Biol. Chem. 256 (1981) 8510-8518. [PMID: 7263666]

3. Arner, R.J., Prabhu, K.S., Thompson, J.T., Hildenbrandt, G.R., Liken, A.D. and Reddy, C.C. myo-Inositol oxygenase: molecular cloning and expression of a unique enzyme that oxidizes myo-inositol and D-chiro-inositol. Biochem. J. 360 (2001) 313-320. [PMID: 11716759]

[EC 1.13.99.2 Transferred entry: benzoate 1,2-dioxygenase - now EC 1.14.12.10 benzoate 1,2-dioxygenase (EC 1.13.99.2 created 1972, deleted 1992)]

EC 1.13.99.3

Accepted name: tryptophan 2'-dioxygenase

Reaction: L-tryptophan + O₂ = (indol-3-yl)glycolaldehyde + CO₂ + NH₃

Other name(s): indole-3-alkane α-hydroxylase; tryptophan side-chain α,β-oxidase; tryptophan side chain oxidase II; tryptophan side-chain oxidase; TSO; indolyl-3-alkan α-hydroxylase; tryptophan side chain oxidase type I; TSO I ; TSO II; tryptophan side chain oxidase

Systematic name: L-tryptophan:oxygen 2'-oxidoreductase (side-chain-cleaving)

Comments: A hemoprotein. Acts on a number of indolyl-3-alkane derivatives, oxidizing the 3-side-chain in the 2'-position. Best substrates were L-tryptophan and 5-hydroxy-L-tryptophan.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 64295-81-4

References:

1. Roberts, J. and Rosenfeld, H.J. Isolation, crystallization, and properties of indolyl-3-alkane α-hydroxylase. A novel tryptophan-metabolizing enzyme. J. Biol. Chem. 252 (1977) 2640-2647. [PMID: 15994]

2. Takai, K., Ushiro, H., Noda, Y., Narumiya, S., Tokuyama, T. and Hayaishi, O. Crystalline hemoprotein from Pseudomonas that catalyzes oxidation of side chain of tryptophan and other indole derivatives. J. Biol. Chem. 252 (1977) 2648-2656. [PMID: 15995]

[EC 1.13.99.4 Transferred entry: 4-chlorophenylacetate 3,4-dioxygenase - now EC 1.14.12.9 4-chlorophenylacetate 3,4-dioxygenase (EC 1.13.99.4 created 1989, deleted 1992)]

[EC 1.13.99.5 Transferred entry: now EC 1.13.11.47, 3,4-dihydroxyquinoline 2,4-dioxygenase (EC 1.13.99.5 created 1999, deleted 2001)]

EC 1.14 ACTING ON PAIRED DONORS, WITH INCORPORATION OR REDUCTION OF MOLECULAR OXYGEN

EC 1.14.11 With 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
EC 1.14.12 With NADH or NADPH as one donor, and incorporation of two atoms of oxygen into one donor
EC 1.14.13 With NAD or NADH as one donor, and incorporation of one atom of oxygen
EC 1.14.14 With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
EC 1.14.15 With reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen
EC 1.14.16 With reduced pteridine as one donor, and incorporation of one atom of oxygen
EC 1.14.17 With reduced ascorbate as one donor, and incorporation of one atom of oxygen
EC 1.14.18 With another compound as one donor, and incorporation of one atom of oxygen
EC 1.14.19 With oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water
EC 1.14.20 With 2-oxoglutarate as one donor, and the other dehydrogenated
EC 1.14.21 With NADH or NADPH as one donor, and the other dehydrogenated
EC 1.14.99 Miscellaneous

Contents

Accepted name: γ-butyrobetaine dioxygenase

Reaction: 4-trimethylammoniobutanoate + 2-oxoglutarate + O₂ = 3-hydroxy-4-trimethylammoniobutanoate + succinate + CO₂

Other name(s): α-butyrobetaine hydroxylase; γ-butyrobetaine hydroxylase; butyrobetaine hydroxylase

Systematic name: 4-trimethylammoniobutanoate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9045-31-2

References:

1. Lindstedt, G. and Lindstedt, S. Cofactor requirements of γ-butyrobetaine hydroxylase from rat liver. J. Biol. Chem. 245 (1970) 4178-4186. [PMID: 4396068]

EC 1.14.11.2

Accepted name: procollagen-proline 4-dioxygenase

Reaction: procollagen L-proline + 2-oxoglutarate + O₂ = procollagen trans-4-hydroxy-L-proline + succinate + CO₂

For diagram of reaction, click here

Other name(s): P4HA (gene name); P4HB (gene name); protocollagen hydroxylase; proline hydroxylase; proline,2-oxoglutarate 4-dioxygenase; collagen proline hydroxylase; hydroxylase, collagen proline; peptidyl proline hydroxylase; proline protocollagen hydroxylase; proline, 2-oxoglutarate dioxygenase; prolyl hydroxylase; prolylprotocollagen dioxygenase; prolylprotocollagen hydroxylase; protocollagen proline 4-hydroxylase; protocollagen proline dioxygenase; protocollagen proline hydroxylase; protocollagen prolyl hydroxylase; prolyl 4-hydroxylase; prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, 4-hydroxylating; procollagen-proline 4-dioxygenase (ambiguous)

Systematic name: procollagen-L-proline,2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate.The enzyme, which is located within the lumen of the endoplasmic reticulum, catalyses the 4-hydroxylation of prolines in -X-Pro-Gly- sequences. The 4-hydroxyproline residues are essential for the formation of the collagen triple helix. The enzyme forms a complex with protein disulfide isomerase and acts not only on procollagen but also on more than 15 other proteins that have collagen-like domains.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9028-06-2

References:

1. Hutton, J.J., Jr., Tappel, A.L. and Udenfriend, S. Cofactor and substrate requirements of collagen proline hydroxylase. Arch. Biochem. Biophys. 118 (1967) 231-240.

2. Kivirikko, K.I. and Prockop, D.J. Purification and partial characterization of the enzyme for the hydroxylation of proline in protocollogen. Arch. Biochem. Biophys. 118 (1967) 611-618.

3. Kivirikko, K.I., Kishida, Y., Sakakibara, S. and Prockop, J. Hydroxylation of (X-Pro-Gly)n by protocollagen proline hydroxylase. Effect of chain length, helical conformation and amino acid sequence in the substrate. Biochim. Biophys. Acta 271 (1972) 347-356. [PMID: 5046811]

4. Berg, R.A. and Prockop, D.J. Affinity column purification of protocollagen proline hydroxylase from chick embryos and further characterization of the enzyme. J. Biol. Chem. 248 (1973) 1175-1182. [PMID: 4346946]

5. John, D.C. and Bulleid, N.J. Prolyl 4-hydroxylase: defective assembly of α-subunit mutants indicates that assembled α-subunits are intramolecularly disulfide bonded. Biochemistry 33 (1994) 14018-14025. [PMID: 7947811]

6. Lamberg, A., Pihlajaniemi, T. and Kivirikko, K.I. Site-directed mutagenesis of the α subunit of human prolyl 4-hydroxylase. Identification of three histidine residues critical for catalytic activity. J. Biol. Chem. 270 (1995) 9926-9931. [PMID: 7730375]

7. Myllyharju, J. and Kivirikko, K.I. Characterization of the iron- and 2-oxoglutarate-binding sites of human prolyl 4-hydroxylase. EMBO J. 16 (1997) 1173-1180. [PMID: 9135134]

8. Kivirikko, K.I. and Myllyharju, J. Prolyl 4-hydroxylases and their protein disulfide isomerase subunit. Matrix Biol 16 (1998) 357-368. [PMID: 9524356]

EC 1.14.11.3

Accepted name: pyrimidine-deoxynucleoside 2'-dioxygenase

Reaction: 2'-deoxyuridine + 2-oxoglutarate + O₂ = uridine + succinate + CO₂

Other name(s): deoxyuridine 2'-dioxygenase; deoxyuridine 2'-hydroxylase; pyrimidine deoxyribonucleoside 2'-hydroxylase; thymidine 2'-dioxygenase; thymidine 2'-hydroxylase; thymidine 2-oxoglutarate dioxygenase; thymidine dioxygenase

Systematic name: 2'-deoxyuridine,2-oxoglutarate:oxygen oxidoreductase (2'-hydroxylating)

Comments: Requires iron((II) and ascorbate. Also acts on thymidine. cf. EC 1.14.11.10, pyrimidine-deoxynucleoside 1'-dioxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9076-89-5

References:

1. Bankel, L., Lindstedt, G. and Lindstedt, S. Thymidine 2'-hydroxylation in Neurospora crassa. J. Biol. Chem. 247 (1972) 6128-6134. [PMID: 4265566]

2. Stubbe, J. Identification of two α-ketoglutarate-dependent dioxygenases in extracts of Rhodotorula glutinis catalyzing deoxyuridine hydroxylation. J. Biol. Chem. 260 (1985) 9972-9975. [PMID: 4040518]

3. Warn-Cramer, B.J., Macrander, L.A. and Abbott, M.T. Markedly different ascorbate dependencies of the sequential α-ketoglutarate dioxygenase reactions catalyzed by an essentially homogeneous thymine 7-hydroxylase from Rhodotorula glutinis. J. Biol. Chem. 258 (1983) 10551-10557. [PMID: 6684117]

EC 1.14.11.4

Accepted name: procollagen-lysine 5-dioxygenase

Reaction: [procollagen]-L-lysine + 2-oxoglutarate + O₂ = [procollagen]-(2S,5R)-5-hydroxy-L-lysine + succinate + CO₂

Other name(s): lysine hydroxylase; lysine,2-oxoglutarate 5-dioxygenase; protocollagen lysine dioxygenase; collagen lysine hydroxylase; lysine-2-oxoglutarate dioxygenase; lysyl hydroxylase; lysylprotocollagen dioxygenase; protocollagen lysyl hydroxylase; peptidyl-lysine, 2-oxoglutarate: oxygen oxidoreductase; peptidyllysine, 2-oxoglutarate:oxygen 5-oxidoreductase; protocollagen lysine hydroxylase

Systematic name: [procollagen]-L-lysine,2-oxoglutarate:oxygen oxidoreductase (5-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9059-25-0

References:

1. Hausmann, E. Cofactor requirements for the enzymatic hydroxylation of lysine in a polypeptide precursor of collagen. Biochim. Biophys. Acta 133 (1967) 591-598. [PMID: 6033801]

2. Rhoads, R.E. and Udenfriend, S. Decarboxylation of α-ketoglutarate coupled to collagen proline hydroxylase. Proc. Natl. Acad. Sci. USA 60 (1968) 1473-1478.

3. Puistola, U., Turpeenniemi-Hujanen, T.M., Myllyla, R. and Kivirikko, K.I. Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. Biochim. Biophys. Acta 611 (1980) 40-50. [PMID: 6766066]

4. Puistola, U., Turpeenniemi-Hujanen, T.M., Myllyla, R. and Kivirikko, K.I. Studies on the lysyl hydroxylase reaction. II. Inhibition kinetics and the reaction mechanism. Biochim. Biophys. Acta 611 (1980) 51-60. [PMID: 6766067]

[EC 1.14.11.5 Deleted entry: 5-hydroxymethyluracil,2-oxoglutarate dioxygenase. Now included with EC 1.14.11.6 thymine dioxygenase (EC 1.14.11.5 created 1972, deleted 1976)]

EC 1.14.11.6

Accepted name: thymine dioxygenase

Reaction: thymine + 2-oxoglutarate + O₂ = 5-hydroxymethyluracil + succinate + CO₂

Other name(s): thymine 7-hydroxylase; 5-hydroxy-methyluracil dioxygenase; 5-hydroxymethyluracil oxygenase

Systematic name: thymine,2-oxoglutarate:oxygen oxidoreductase (7-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. Also acts on 5-hydroxymethyluracil to oxidize its -CH₂OH group first to -CHO and then to -COOH.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37256-67-0

References:

1. Bankel, L., Holme, E., Lindstedt, G. and Lindstedt, S. Oxygenases involved in thymine and thymidine metabolism in Neurospora crassa. FEBS Lett. 21 (1972) 135-138.

2. Liu, C.-K., Hsu, C.-A. and Abbott, M.T. Catalysis of three sequential dioxygenase reactions by thymine 7-hydroxylase. Arch. Biochem. Biophys. 159 (1973) 180-187. [PMID: 4274083]

3. Warn-Cramer, B.J., Macrander, L.A. and Abbott, M.T. Markedly different ascorbate dependencies of the sequential α-ketoglutarate dioxygenase reactions catalyzed by an essentially homogeneous thymine 7-hydroxylase from Rhodotorula glutinis. J. Biol. Chem. 258 (1983) 10551-10557. [PMID: 6684117]

EC 1.14.11.7

Accepted name: procollagen-proline 3-dioxygenase

Reaction: [procollagen]-L-proline + 2-oxoglutarate + O₂ = [procollagen]-trans-3-hydroxy-L-proline + succinate + CO₂

For diagram of reaction click here

Other name(s): proline,2-oxoglutarate 3-dioxygenase; prolyl 3-hydroxylase; protocollagen proline 3-hydroxylase; prolyl-4-hydroxyprolyl-glycyl-peptide, 2-oxoglutarate: oxygen oxidoreductase, 3-hydroxylating

Systematic name: [procollagen]-L-proline,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme forms a complex with protein disulfide isomerase, and is located in the endoplasmic reticulum. It modifies proline residues within the procollagen peptide of certain collagen types. The modification is essential for proper collagen triple helix formation.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 63551-75-7

References:

1. Risteli, J., Tryggvason, K. and Kivirikko, K.I. Prolyl 3-hydroxylase: partial characterization of the enzyme from rat kidney cortex. Eur. J. Biochem. 73 (1977) 485-492. [PMID: 191255]

2. Risteli, J., Tryggvason, K. and Kivirikko, K.I. A rapid assay for prolyl 3-hydroxylase activity. Anal. Biochem. 84 (1978) 423-431. [PMID: 204218]

3. Vranka, J.A., Sakai, L.Y. and Bachinger, H.P. Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymes. J. Biol. Chem. 279 (2004) 23615-23621. [PMID: 15044469]

4. Tiainen, P., Pasanen, A., Sormunen, R. and Myllyharju, J. Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV. J. Biol. Chem. 283 (2008) 19432-19439. [PMID: 18487197]

EC 1.14.11.8

Accepted name: trimethyllysine dioxygenase

Reaction: N⁶,N⁶,N⁶-trimethyl-L-lysine + 2-oxoglutarate + O₂ = (3S)-3-hydroxy-N⁶,N⁶,N⁶-trimethyl-L-lysine + succinate + CO₂

Other name(s): trimethyllysine α-ketoglutarate dioxygenase; TML-α-ketoglutarate dioxygenase; TML hydroxylase; 6-N,6-N,6-N-trimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Systematic name: N⁶,N⁶,N⁶-trimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 74622-49-4

References:

1. Hulse, J.D., Ellis, S.R. and Henderson, L.M. Carnitine biosynthesis. β-Hydroxylation of trimethyllysine by an α-ketoglutarate-dependent mitochondrial dioxygenase. J. Biol. Chem. 253 (1978) 1654-1659. [PMID: 627563]

EC 1.14.11.9

Accepted name: flavanone 3-dioxygenase

Reaction: a (2S)-flavan-4-one + 2-oxoglutarate + O₂ = a (2R,3R)-dihydroflavonol + succinate + CO₂

For diagram of reaction click here and mechanism click here.

Other name(s): naringenin 3-hydroxylase; flavanone 3-hydroxylase; flavanone 3β-hydroxylase; flavanone synthase I; (2S)-flavanone 3-hydroxylase; naringenin,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating); F₃H; flavanone,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Systematic name: (2S)-flavan-4-one,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. This plant enzyme catalyses an early step in the flavonoid biosynthesis pathway, leading to the production of flavanols and anthocyanins. Substrates include (2S)-naringenin, (2S)-eriodictyol, (2S)-dihydrotricetin and (2S)-pinocembrin. Some enzymes are bifuctional and also catalyse EC 1.14.20.6, flavonol synthase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 75991-43-4

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. Charrier, B., Coronado, C., Kondorosi, A. and Ratet, P. Molecular characterization and expression of alfalfa (Medicago sativa L.) flavanone-3-hydroxylase and dihydroflavonol-4-reductase encoding genes. Plant Mol. Biol. 29 (1995) 773-786. [PMID: 8541503]

3. Pelletier, M.K. and Shirley, B.W. Analysis of flavanone 3-hydroxylase in Arabidopsis seedlings. Coordinate regulation with chalcone synthase and chalcone isomerase. Plant Physiol. 111 (1996) 339-345. [PMID: 8685272]

4. Wellmann, F., Matern, U. and Lukačin, R. Significance of C-terminal sequence elements for Petunia flavanone 3β-hydroxylase activity. FEBS Lett. 561 (2004) 149-154. [PMID: 15013767]

5. Jin, Z., Grotewold, E., Qu, W., Fu, G. and Zhao, D. Cloning and characterization of a flavanone 3-hydroxylase gene from Saussurea medusa. DNA Seq 16 (2005) 121-129. [PMID: 16147863]

6. Shen, G., Pang, Y., Wu, W., Deng, Z., Zhao, L., Cao, Y., Sun, X. and Tang, K. Cloning and characterization of a flavanone 3-hydroxylase gene from Ginkgo biloba. Biosci Rep 26 (2006) 19-29. [PMID: 16779664]

EC 1.14.11.10

Accepted name: pyrimidine-deoxynucleoside 1'-dioxygenase

Reaction: 2'-deoxyuridine + 2-oxoglutarate + O₂ = uracil + 2-deoxyribonolactone + succinate + CO₂

Other name(s): deoxyuridine-uridine 1'-dioxygenase

Systematic name: 2'-deoxyuridine,2-oxoglutarate:oxygen oxidoreductase (1'-hydroxylating)

Comments: Requires iron((II) and ascorbate. cf. EC 1.14.11.3, pyrimidine-deoxynucleoside 2'-dioxygenase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 98865-52-2

References:

1. Stubbe, J. Identification of two α-ketoglutarate-dependent dioxygenases in extracts of Rhodotorula glutinis catalyzing deoxyuridine hydroxylation. J. Biol. Chem. 260 (1985) 9972-9975. [PMID: 4040518]

EC 1.14.11.11

Accepted name: hyoscyamine (6S)-dioxygenase

Reaction: L-hyoscyamine + 2-oxoglutarate + O₂ = (6S)-hydroxyhyoscyamine + succinate + CO₂

For diagram of reaction, click here.

Other name(s): hyoscyamine 6β-hydroxylase; hyoscyamine 6β-dioxygenase; hyoscyamine 6-hydroxylase

Systematic name: L-hyoscyamine,2-oxoglutarate:oxygen oxidoreductase [(6S)-hydroxylating]

Comments: Requires Fe²⁺ and ascorbate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 103865-33-4

References:

1. Hashimoto, T. and Yamada, Y. Hyoscyamine 6β-hydroxylase, a 2-oxoglutarate-dependent dioxygenase, in alkaloid-producing root cultures. Plant Physiol. 81 (1986) 619-625.

EC 1.14.11.12

Accepted name: gibberellin-44 dioxygenase

Reaction: gibberellin 44 + 2-oxoglutarate + O₂ = gibberellin 19 + succinate + CO₂

For reaction pathway click here.

Other name(s): oxygenase, gibberellin A44 oxidase; (gibberellin-44), 2-oxoglutarate:oxygen oxidoreductase

Systematic name: (gibberellin-44),2-oxoglutarate:oxygen oxidoreductase

Comments: Requires Fe²⁺.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 112198-85-3

References:

1. Gilmour, S.J., Bleecker, A.B. and Zeevaart, J.A.D. Partial-purification of gibberellin oxidases from spinach leaves. Plant Physiol. 85 (1987) 87-90.

EC 1.14.11.13

Accepted name: gibberellin 2β-dioxygenase

Reaction: gibberellin 1 + 2-oxoglutarate + O₂ = 2β-hydroxygibberellin 1 + succinate + CO₂

For reaction pathway click here.

Other name(s): gibberellin 2β-hydroxylase

Systematic name: (gibberellin-1),2-oxoglutarate:oxygen oxidoreductase (2β-hydroxylating)

Comments: Also acts on a number of other gibberellins.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 85713-20-8

References:

1. Smith, V.A. and MacMillan, J. The partial-purification and characterization of gibberellin 2β-hydroxylases from seeds of Pisum sativum. Planta 167 (1986) 9-18.

[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 1.14.11.15

Accepted name: gibberellin 3β-dioxygenase

Reaction: gibberellin 20 + 2-oxoglutarate + O₂ = gibberellin 1 + succinate + CO₂

For reaction pathway click here.

Other name(s): gibberellin 3β-hydroxylase; (gibberrellin-20),2-oxoglutarate: oxygen oxidoreductase (3β-hydroxylating)

Systematic name: (gibberellin-20),2-oxoglutarate:oxygen oxidoreductase (3β-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 120860-89-1

References:

1. Kwak, S.-S., Kamiya, Y., Sakurai, A., Takahishi, N. and Graebe, J.E. Partial-purification and characterization of gibberellin 3β-hydroxylase from immature seeds of Phaseolus vulgaris L. Plant Cell Physiol. 29 (1988) 935-943.

EC 1.14.11.16

Accepted name: peptide-aspartate β-dioxygenase

Reaction: peptide-L-aspartate + 2-oxoglutarate + O₂ = peptide-3-hydroxy-L-aspartate + succinate + CO₂

Other name(s): aspartate β-hydroxylase; aspartylpeptide β-dioxygenase

Systematic name: peptide-L-aspartate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe²⁺. Some vitamin K-dependent coagulation factors, as well as synthetic peptides based on the structure of the first epidermal growth factor domain of human coagulation factor IX or X, can act as acceptors.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 122544-66-5

References:

1. Gronke, R.S., Welsch, D.J., VanDusen, W.J., Garsky, V.M., Sardana, M.K., Stern, A.M. and Friedman, P.A. Partial purification and characterization of bovine liver aspartyl β-hydroxylase. J. Biol. Chem. 265 (1990) 8558-8565. [PMID: 2187868]

EC 1.14.11.17

Accepted name: taurine dioxygenase

Reaction: taurine + 2-oxoglutarate + O₂ = sulfite + aminoacetaldehyde + succinate + CO₂

Other name(s) 2-aminoethanesulfonate dioxygenase; α-ketoglutarate-dependent taurine dioxygenase

Systematic name: taurine, 2-oxoglutarate::oxygen oxidoreductase (sulfite-forming)

Comments: Requires Fe^II. The enzyme from Escherichia coli also acts on pentanesulfonate, 3-(N-morpholino)propanesulfonate and 2-(1,3-dioxoisoindolin-2-yl)ethanesulfonate, but at lower rates.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 197809-75-9

References:

1. Eichhorn, E., Van Der Poeg, J.R., Kertesz, M.A. and Leisinger, T. Characterization of α-ketoglutarate-dependent taurine dioxygenase from Escherichia coli. J.Biol. Chem. 272 (1997) 23031-23036. [PMID: 9287300]

EC 1.14.11.18

Accepted name: phytanoyl-CoA dioxygenase

Reaction: phytanoyl-CoA + 2-oxoglutarate + O₂ = 2-hydroxyphytanoyl-CoA + succinate + CO₂

Glossary entries
phytanate: 3,7,11,15-tetramethylhexadecanoate

Other name(s): phytanoyl-CoA hydroxylase

Systematic name: phytanoyl-CoA, 2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating)

Comments: Part of the peroxisomal phytanic acid α-oxidation pathway. Requires Fe²⁺ and ascorbate.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 185402-46-4

References:

1. Jansen, G.A., Mihalik, S.J., Watkins, P.A., Jakobs, C., Moser, H.W. and Wanders, R.J.A. Characterization of phytanoyl-CoA hydroxylase in human liver and activity measurements in patients with peroxisomal disorders. Clin. Chim. Acta 271 (1998) 203-211. [PMID: 9565335]

2. Jansen, G.A., Mihalik, S.J., Watkins, P.A., Moser, H.W., Jakobs, C., Denis, S. and Wanders, R.J.A. Phytanoyl-CoA hydroxylase is present in human liver, located in peroxisomes, and deficient in Zellweger syndrome: direct, unequivocal evidence for the new, revised pathway of phytanic acid α-oxidation in humans. Biochem. Biophys. Res. Commun. 229 (1996) 205-210. [PMID: 8954107]

3. Jansen, G.A., Ofman, R., Ferdinandusse, S., Ijlst, L., Muijsers, A.O., Skjeldal, O.H., Stokke, O., Jakobs, C., Besley, G.T.N., Wraith, J.E. and Wanders, R.J.A. Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene. Nat. Genet. 17 (1997) 190-193. [PMID: 9326940]

4. Mihalik, S.J., Rainville, A.M. and Watkins, P.A. Phytanic acid α-oxidation in rat liver peroxisomes. Production of α-hydroxyphytanoyl-CoA and formate is enhanced by dioxygenase cofactors. Eur. J. Biochem. 232 (1995) 545-551.

5. Mihalik, S.J., Morrell, J.C., Kim, D., Sacksteder, K.A., Watkins, P.A. and Gould, S.J. Identification of PAHX, a Refsum disease gene. Nat. Genet. 17 (1997) 185-189. [PMID: 9326939]

[EC 1.14.11.19 Transferred entry: anthocyanidin synthase. Now EC 1.14.20.4, anthocyanidin synthase (EC 1.14.11.19 created 2001, modified 2017, deleted 2018)]

EC 1.14.11.20

Accepted name: deacetoxyvindoline 4-hydroxylase

Reaction: deacetoxyvindoline + 2-oxoglutarate + O₂ = deacetylvindoline + succinate + CO₂

For reaction pathway click here.

Other name(s): desacetoxyvindoline 4-hydroxylase; desacetyoxyvindoline-17-hydroxylase; D17H; desacetoxyvindoline,2-oxoglutarate:oxygen oxidoreductase (4β-hydroxylating)

Systematic name: deacetoxyvindoline,2-oxoglutarate:oxygen oxidoreductase (4β-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. Also acts on 3-hydroxy-16-methoxy-2,3-dihydrotabersonine and to a lesser extent on 16-methoxy-2,3-dihydrotabersonine.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 132084-83-4

References:

1. De Carolis, E., Chan, F., Balsevich, J. and De Luca, V. Isolation and characterization of a 2-oxoglutarate dependent dioxygenase involved in the 2nd-to-last step in vindoline biosynthesis Plant Physiol. 94 (1990) 1323-1329.

2. De Carolis, E. and De Luca, V. Purification, characterization, and kinetic analysis of a 2-oxoglutarate-dependent dioxygenase involved in vindoline biosynthesis from Catharanthus roseus. J. Biol. Chem. 268 (1993) 5504-5511. [PMID: 8449913]

3. Vazquez-Flota, F.A. and De Luca, V. Developmental and light regulation of desacetoxyvindoline 4-hydroxylase in Catharanthus roseus (L.) G. Don. Evidence of a multilevel regulatory mechanism. Plant Physiol. 117 (1998) 1351-1361. [PMID: 9701591]

EC 1.14.11.21

Accepted name: clavaminate synthase

Reaction: (1) deoxyamidinoproclavaminate + 2-oxoglutarate + O₂ = amidinoproclavaminate + succinate + CO₂

(2) proclavaminate + 2-oxoglutarate + O₂ = dihydroclavaminate + succinate + CO₂ + H₂O

(3) dihydroclavaminate + 2-oxoglutarate + O₂ = clavaminate + succinate + CO₂ + H₂O

For diagram click here.

Other name(s): clavaminate synthase 2; clavaminic acid synthase

Systematic name: deoxyamidinoproclavaminate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Contains nonheme iron. Catalyses three separate oxidative reactions in the pathway for the biosythesis of the β-lactamase inhibitor clavulanate in Streptomyces clavuligerus. The first step (hydroxylation) is separated from the latter two (oxidative cyclization and desaturation) by the action of EC 3.5.3.22, proclavaminate amidinohydrolase. The three reactions are all catalysed at the same nonheme iron site.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 122799-56-8

References:

1. Salowe, S.P., Krol, W.J., Iwatareuyl, D. and Townsend, C.A. Elucidation of the order of oxidations and identification of an intermediate in the multistep clavaminate synthase reaction. Biochemistry 30 (1991) 2281-2292. [PMID: 1998687]

2. Zhou, J., Gunsior, M., Bachmann, B.O., Townsend, C.A. and Solomon, E.I. Substrate binding to the α-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: Coupling mechanism of oxidative decarboxylation and hydroxylation. J. Am. Chem. Soc. 120 (1998) 13539-13540.

3. Zhang, Z.H., Ren, J.S., Stammers, D.K., Baldwin, J.E., Harlos, K. and Schofield, C.J. Structural origins of the selectivity of the trifunctional oxygenase clavaminic acid synthase. Nat. Struct. Biol. 7 (2000) 127-133. [PMID: 10655615]

4. Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A. and Solomon, E.I. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional α-KG-dependent non-heme iron enzyme: Correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123 (2001) 7388-7398.

5. Townsend, C.A. New reactions in clavulanic acid biosynthesis. Curr. Opin. Chem. Biol. 6 (2002) 583-589. [PMID: 12413541]

[EC 1.14.11.22 Transferred entry: flavone synthase. Now EC 1.14.20.5, flavone synthase (EC 1.14.11.22 created 2004, deleted 2018)]

[EC 1.14.11.23 Transferred entry: flavonol synthase. Now EC 1.14.20.6, flavonol synthase (EC 1.14.11.23 created 2004, deleted 2018)]

EC 1.14.11.24

Accepted name: 2'-deoxymugineic-acid 2'-dioxygenase

Reaction: 2'-deoxymugineic acid + 2-oxoglutarate + O₂ = mugineic acid + succinate + CO₂

For diagram click here.

Other name(s): IDS3

Systematic name: 2'-deoxymugineic acid,2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating)

Comments: Requires iron(II). It is also likely that this enzyme can catalyse the hydroxylation of 3-epihydroxy-2'-deoxymugineic acid to form 3-epihydroxymugineic acid.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 133758-62-0

References:

1. Nakanishi, H., Yamaguchi, H., Sasakuma, T., Nishizawa, N.K. and Mori, S. Two dioxygenase genes, Ids3 and Ids2, from Hordeum vulgare are involved in the biosynthesis of mugineic acid family phytosiderophores. Plant Mol. Biol. 44 (2000) 199-207. [PMID: 11117263]

2. Kobayashi, T., Nakanishi, H., Takahashi, M., Kawasaki, S., Nishizawa, N.K. and Mori, S. In vivo evidence that Ids3 from Hordeum vulgare encodes a dioxygenase that converts 2'-deoxymugineic acid to mugineic acid in transgenic rice. Planta 212 (2001) 864-871. [PMID: 11346963]

EC 1.14.11.25

Accepted name: mugineic-acid 3-dioxygenase

Reaction: (1) mugineic acid + 2-oxoglutarate + O₂ = 3-epihydroxymugineic acid + succinate + CO₂

(2) 2'-deoxymugineic acid + 2-oxoglutarate + O₂ = 3-epihydroxy-2'-deoxymugineic acid + succinate + CO₂

For diagram click here.

Other name(s): IDS2

Systematic name: mugineic acid,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires iron(II).

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

References:

1. Nakanishi, H., Yamaguchi, H., Sasakuma, T., Nishizawa, N.K. and Mori, S. Two dioxygenase genes, Ids3 and Ids2, from Hordeum vulgare are involved in the biosynthesis of mugineic acid family phytosiderophores. Plant Mol. Biol. 44 (2000) 199-207. [PMID: 11117263]

2. Okumura, N., Nishizawa, N.K., Umehara, Y., Ohata, T., Nakanishi, H., Yamaguchi, T., Chino, M. and Mori. S. A dioxygenase gene (Ids2) expressed under iron deficiency conditions in the roots of Hordeum vulgare. Plant Mol. Biol. 25 (1994) 705-719. [PMID: 8061321]

EC 1.14.11.26

Accepted name: deacetoxycephalosporin-C hydroxylase

Reaction: deacetoxycephalosporin C + 2-oxoglutarate + O₂ = deacetylcephalosporin C + succinate + CO₂

For diagram click here.

Other name(s): deacetylcephalosporin C synthase; 3'-methylcephem hydroxylase; DACS; DAOC hydroxylase; deacetoxycephalosporin C hydroxylase

Systematic name: deacetoxycephalosporin-C,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires iron(II). The enzyme can also use 3-exomethylenecephalosporin C as a substrate to form deacetoxycephalosporin C, although more slowly [2]. In Acremonium chrysogenum, the enzyme forms part of a bifunctional protein along with EC 1.14.20.1, deactoxycephalosporin-C synthase. It is a separate enzyme in Streptomyces clavuligerus.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 69772-89-0

References:

1. Dotzlaf, J.E. and Yeh, W.K. Copurification and characterization of deacetoxycephalosporin C synthetase/hydroxylase from Cephalosporium acremonium. J. Bacteriol. 169 (1987) 1611-1618. [PMID: 3558321]

2. Baker, B.J., Dotzlaf, J.E. and Yeh, W.K. Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus. Purification, characterization, bifunctionality, and evolutionary implication. J. Biol. Chem. 266 (1991) 5087-5093. [PMID: 2002049]

3. Coque, J.J., Enguita, F.J., Cardoza, R.E., Martin, J.F. and Liras, P. Characterization of the cefF gene of Nocardia lactamdurans encoding a 3'-methylcephem hydroxylase different from the 7-cephem hydroxylase. Appl. Microbiol. Biotechnol. 44 (1996) 605-609. [PMID: 8703431]

4. Ghag, S.K., Brems, D.N., Hassell, T.C. and Yeh, W.K. Refolding and purification of Cephalosporium acremonium deacetoxycephalosporin C synthetase/hydroxylase from granules of recombinant Escherichia coli. Biotechnol. Appl. Biochem. 24 (1996) 109-119. [PMID: 8865604]

5. Lloyd, M.D., Lipscomb, S.J., Hewitson, K.S., Hensgens, C.M., Baldwin, J.E. and Schofield, C.J. Controlling the substrate selectivity of deacetoxycephalosporin/deacetylcephalosporin C synthase. J. Biol. Chem. 279 (2004) 15420-15426. [PMID: 14734549]

6. Wu, X.B., Fan, K.Q., Wang, Q.H. and Yang, K.Q. C-terminus mutations of Acremonium chrysogenum deacetoxy/deacetylcephalosporin C synthase with improved activity toward penicillin analogs. FEMS Microbiol. Lett. 246 (2005) 103-110. [PMID: 15869968]

7. Martín, J.F., Gutiérrez, S., Fernández, F.J., Velasco, J., Fierro, F., Marcos, A.T. and Kosalkova, K. Expression of genes and processing of enzymes for the biosynthesis of penicillins and cephalosporins. Antonie Van Leeuwenhoek 65 (1994) 227-43. [PMID: 7847890]

EC 1.14.11.27

Accepted name: [histone H3]-dimethyl-L-lysine³⁶ demethylase

Reaction: a [histone H3]-N⁶,N⁶-dimethyl-L-lysine³⁶ + 2 2-oxoglutarate + 2 O₂ = a [histone H3]-L-lysine³⁶ + 2 succinate + 2 formaldehyde + 2 CO₂ (overall reaction)
(1a) a [histone H3]-N⁶,N⁶-dimethyl-L-lysine³⁶ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶-methyl-L-lysine³⁶ + succinate + formaldehyde + CO₂
(1b) a [histone H3]-N⁶-methyl-L-lysine³⁶ + 2-oxoglutarate + O₂ = a [histone H3]-L-lysine³⁶ + succinate + formaldehyde + CO₂

Other name(s): KDM2A (gene name); KDM2B (gene name); JHDM1A (gene name); JHDM1B (gene name); JmjC domain-containing histone demethylase 1A; H3-K36-specific demethylase (ambiguous); histone-lysine (H3-K36) demethylase (ambiguous); histone demethylase (ambiguous); protein-6-N,6-N-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase; protein-N⁶,N⁶-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase; [histone-H3]-lysine³⁶ demethylase

Systematic name: [histone H3]-N⁶,N⁶-dimethyl-L-lysine³⁶,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron(II). Of the seven potential methylation sites in histones H3 (K4, K9, K27, K36, K79) and H4 (K20, R3) from HeLa cells, the enzyme is specific for Lys³⁶. Lysine residues exist in three methylation states (mono-, di- and trimethylated). The enzyme preferentially demethylates the dimethyl form of Lys³⁶ (K36me2), which is its natural substrate, to form the monomethylated and unmethylated forms of Lys³⁶. It can also demethylate monomethylated (but not the trimethylated) Lys³⁶. cf. EC 1.14.11.69, [histone H3]-trimethyl-L-lysine³⁶ demethylase.

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

References:

1. Tsukada, Y., Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P. and Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature 439 (2006) 811-816. [PMID: 16362057]

EC 1.14.11.28

Accepted name: proline 3-hydroxylase

Reaction: L-proline + 2-oxoglutarate + O₂ = cis-3-hydroxy-L-proline + succinate + CO₂

For diagram click here.

Other name(s): P-3-H

Systematic name: L-proline,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires iron(II) for activity. Unlike the proline hydroxylases involved in collagen biosynthesis [EC 1.14.11.2 (procollagen-proline dioxygenase) and EC 1.14.11.7 (procollagen-proline 3-dioxygenase)], this enzyme does not require ascorbate for activity although it does increase the activity of the enzyme [2]. The enzyme is specific for L-proline as D-proline, trans-4-hydroxy-L-proline, cis-4-hydroxy-L-proline and 3,4-dehydro-DL-proline are not substrates [2].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 162995-24-6

References:

1. Mori, H., Shibasaki, T., Uozaki, Y., Ochiai, K. and Ozaki, A. Detection of novel proline 3-hydroxylase activities in Streptomyces and Bacillus spp. by regio- and stereospecific hydroxylation of L-proline. Appl. Environ. Microbiol. 62 (1996) 1903-1907. [PMID: 16535329]

2. Mori, H., Shibasaki, T., Yano, K. and Ozaki, A. Purification and cloning of a proline 3-hydroxylase, a novel enzyme which hydroxylates free L-proline to cis-3-hydroxy-L-proline. J. Bacteriol. 179 (1997) 5677-5683. [PMID: 9294421]

3. Clifton, I.J., Hsueh, L.C., Baldwin, J.E., Harlos, K. and Schofield, C.J. Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. Eur. J. Biochem. 268 (2001) 6625-6636. [PMID: 11737217]

EC 1.14.11.29

Accepted name: hypoxia-inducible factor-proline dioxygenase

Reaction: hypoxia-inducible factor-L-proline + 2-oxoglutarate + O₂ = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO₂

Other name(s): HIF hydroxylase

Systematic name: hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

Comments: Contains iron, and requires ascorbate. Specifically hydroxylates a proline residue in HIF-α, the α subunit of the transcriptional regulator HIF (hypoxia-inducible factor), which targets HIF for proteasomal destruction. The requirement of oxygen for the hydroxylation reaction enables animals to respond to hypoxia.

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

References:

1. Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Kriegsheim Av, Hebestreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W. and Ratcliffe, P.J. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O₂-regulated prolyl hydroxylation. Science 292 (2001) 468-472. [PMID: 11292861]

2. Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J.M., Lane, W.S. and Kaelin , W.G., Jr. HIFα targeted for VHL-mediated destruction by proline hydroxylation: implications for O₂ sensing. Science 292 (2001) 464-468. [PMID: 11292862]

3. Bruick, R.K. and McKnight, S.L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294 (2001) 1337-1340. [PMID: 11598268]

4. Epstein, A.C., Gleadle, J.M., McNeill, L.A., Hewitson, K.S., O'Rourke, J., Mole, D.R., Mukherji, M., Metzen, E., Wilson, M.I., Dhanda, A., Tian, Y.M., Masson, N., Hamilton, D.L., Jaakkola, P., Barstead, R., Hodgkin, J., Maxwell, P.H., Pugh, C.W., Schofield, C.J. and Ratcliffe, P.J. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107 (2001) 43-54. [PMID: 11595184]

5. Oehme, F., Ellinghaus, P., Kolkhof, P., Smith, T.J., Ramakrishnan, S., Hutter, J., Schramm, M. and Flamme, I. Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors. Biochem. Biophys. Res. Commun. 296 (2002) 343-349. [PMID: 12163023]

6. McNeill, L.A., Hewitson, K.S., Gleadle, J.M., Horsfall, L.E., Oldham, N.J., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J. and Schofield, C.J. The use of dioxygen by HIF prolyl hydroxylase (PHD1). Bioorg. Med. Chem. Lett. 12 (2002) 1547-1550. [PMID: 12039559]

EC 1.14.11.30

Accepted name: hypoxia-inducible factor-asparagine dioxygenase

Reaction: hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O₂ = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO₂

Other name(s): HIF hydroxylase

Systematic name: hypoxia-inducible factor-L-asparagine, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

Comments: Contains iron, and requires ascorbate. Catalyses hydroxylation of an asparagine in the C-terminal transcriptional activation domain of HIF-α, the α subunit of the transcriptional regulator HIF (hypoxia-inducible factor), which reduces its interaction with the transcriptional coactivator protein p300. The requirement of oxygen for the hydroxylation reaction enables animals to respond to hypoxia.

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

References:

1. Mahon, P.C., Hirota, K. and Semenza, G.L. FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 15 (2001) 2675-2686. [PMID: 11641274]

2. Hewitson, K.S., McNeill, L.A., Riordan, M.V., Tian, Y.M., Bullock, A.N., Welford, R.W., Elkins, J.M., Oldham, N.J., Bhattacharya, S., Gleadle, J.M., Ratcliffe, P.J., Pugh, C.W. and Schofield, C.J. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J. Biol. Chem. 277 (2002) 26351-26355. [PMID: 12042299]

4. Lando, D., Peet, D.J., Whelan, D.A., Gorman, J.J. and Whitelaw, M.L. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295 (2002) 858-861. [PMID: 11823643]

5. Koivunen, P., Hirsila, M., Gunzler, V., Kivirikko, K.I. and Myllyharju, J. Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases. J. Biol. Chem. 279 (2004) 9899-9904. [PMID: 14701857]

6. Elkins, J.M., Hewitson, K.S., McNeill, L.A., Seibel, J.F., Schlemminger, I., Pugh, C.W., Ratcliffe, P.J. and Schofield, C.J. Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 α. J. Biol. Chem. 278 (2003) 1802-1806. [PMID: 12446723]

EC 1.14.11.31

Accepted name: thebaine 6-O-demethylase

Reaction: thebaine + 2-oxoglutarate + O₂ = neopinone + formaldehyde + succinate + CO₂

Other name(s): T6ODM

Systematic name: thebaine,2-oxoglutarate:oxygen oxidoreductase (6-O-demethylating)

Comments: Requires Fe²⁺. Catalyses a step in morphine biosynthesis. The product neopinione spontaneously rearranges to the more stable codeinone. The enzyme also catalyses the 6-O-demethylation of oripavine to morphinone, with lower efficiency.

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

References:

1. Hagel, J.M. and Facchini, P.J. Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy. Nat. Chem. Biol. 6 (2010) 273-275. [PMID: 20228795]

EC 1.14.11.32

Accepted name: codeine 3-O-demethylase

Reaction: codeine + 2-oxoglutarate + O₂ = morphine + formaldehyde + succinate + CO₂

Other name(s): codeine O-demethylase; CODM

Systematic name: codeine,2-oxoglutarate:oxygen oxidoreductase (3-O-demethylating)

Comments: Requires Fe²⁺. Catalyses a step in morphine biosynthesis. The enzyme also catalyses the 3-O-demethylation of thebaine to oripavine, with lower efficiency.

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

References:

1. Hagel, J.M. and Facchini, P.J. Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy. Nat. Chem. Biol. 6 (2010) 273-275. [PMID: 20228795]

EC 1.14.11.33

Accepted name: DNA oxidative demethylase

Reaction: DNA-base-CH₃ + 2-oxoglutarate + O₂ = DNA-base + formaldehyde + succinate + CO₂

Other name(s): alkylated DNA repair protein; α-ketoglutarate-dependent dioxygenase ABH1; alkB (gene name)

Systematic name: Methyl DNA-base, 2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)

Comments: Contains iron; activity is slightly stimulated by ascorbate. Catalyses oxidative demethylation of the DNA base lesions N¹-methyladenine, N³-methylcytosine, N¹-methylguanine, and N³-methylthymine. It works better on single-stranded DNA (ssDNA) and is capable of repairing damaged bases in RNA.

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

References:

1. Falnes, P.O., Johansen, R.F. and Seeberg, E. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 419 (2002) 178-182. [PMID: 12226668]

2. Yi, C., Yang, C.G. and He, C. A non-heme iron-mediated chemical demethylation in DNA and RNA. Acc. Chem. Res. 42 (2009) 519-529. [PMID: 19852088]

3. Yi, C., Jia, G., Hou, G., Dai, Q., Zhang, W., Zheng, G., Jian, X., Yang, C.G., Cui, Q. and He, C. Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase. Nature 468 (2010) 330-333. [PMID: 21068844]

[EC 1.14.11.34 Transferred entry: 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming). Now EC 1.14.20.7, 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming) (EC 1.14.11.34 created 2011, deleted 2018)]

EC 1.14.11.35

Accepted name: 1-deoxypentalenic acid 11β-hydroxylase

Reaction: 1-deoxypentalenate + 2-oxoglutarate + O₂ = 1-deoxy-11β-hydroxypentalenate + succinate + CO₂

For diagram of reaction click here.

Glossary: 1-deoxypentalenate = (1R,3aR,5aS,8aR)-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate
1-deoxy-11β-hydroxypentalenate = (1S,2R,3aR,5aS,8aR)-2-hydroxy-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate

Other name(s): ptlH (gene name); sav2991 (gene name); pntH (gene name)

Systematic name: 1-deoxypentalenic acid,2-oxoglutarate:oxygen oxidoreductase

Comments: The enzyme requires iron((II) and ascorbate. Isolated from the bacterium Streptomyces avermitilis. Part of the pathway for pentalenolactone biosynthesis.

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

References:

1. You, Z., Omura, S., Ikeda, H. and Cane, D.E. Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlH, a non-heme iron dioxygenase of Streptomyces avermitilis. J. Am. Chem. Soc. 128 (2006) 6566-6567. [PMID: 16704250]

2. You, Z., Omura, S., Ikeda, H., Cane, D.E. and Jogl, G. Crystal structure of the non-heme iron dioxygenase PtlH in pentalenolactone biosynthesis. J. Biol. Chem. 282 (2007) 36552-36560. [PMID: 17942405]

EC 1.14.11.36

Accepted name: pentalenolactone F synthase

Reaction: pentalenolactone D + 2 2-oxoglutarate + 2 O₂ = pentalenolactone F + 2 succinate + 2 CO₂ + H₂O (overall reaction)
(1a) pentalenolactone D + 2-oxoglutarate + O₂ = pentalenolactone E + succinate + CO₂ + H₂O
(1b) pentalenolactone E + 2-oxoglutarate + O₂ = pentalenolactone F + succinate + CO₂

For diagram of reaction click here.

Glossary: pentalenolactone D = (1S,4aR,6aS,9aR)-1,8,8-trimethyl-2-oxo-1,2,4,4a,6a,7,8,9-octahydropentaleno[1,6a-c]pyran-5-carboxylate
pentalenolactone E = (4aR,6aS,9aR)-8,8-dimethyl-1-methylene-2-oxo-1,2,4,4a,6a,7,8,9-octahydropentaleno[1,6a-c]pyran-5-carboxylate
pentalenolactone F = (1'R,4'aR,6'aS,9'aR)-8',8'-dimethyl-2'-oxo-4',4'a,6'a,8',9'-hexahydrospiro[oxirane-2,1'-pentaleno[1,6a-c]pyran]-5'-carboxylic acid

Other name(s): penD (gene name); pntD (gene name); ptlD (gene name)

Systematic name: pentalenolactone-D,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron((II) and ascorbate. Isolated from the bacteria Streptomyces exfoliatus, Streptomyces arenae and Streptomyces avermitilis. Part of the pentalenolactone biosynthesis pathway.

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

References:

1. Seo, M.J., Zhu, D., Endo, S., Ikeda, H. and Cane, D.E. Genome mining in Streptomyces. Elucidation of the role of Baeyer-Villiger monooxygenases and non-heme iron-dependent dehydrogenase/oxygenases in the final steps of the biosynthesis of pentalenolactone and neopentalenolactone. Biochemistry 50 (2011) 1739-1754. [PMID: 21250661]

EC 1.14.11.37

Accepted name: kanamycin B dioxygenase

Reaction: kanamycin B + 2-oxoglutarate + O₂ = 2′-dehydrokanamycin A + succinate + NH₃ + CO₂

For diagram of reaction, click here

Other name(s): kanJ (gene name)

Systematic name: kanamycin-B,2-oxoglutarate:oxygen oxidoreductase (deaminating, 2′-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. Found in the bacterium Streptomyces kanamyceticus where it is involved in the conversion of the aminoglycoside antibiotic kanamycin B to kanamycin A.

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

References:

1. Sucipto, H., Kudo, F. and Eguchi, T. The last step of kanamycin biosynthesis: unique deamination reaction catalyzed by the α-ketoglutarate-dependent nonheme iron dioxygenase KanJ and the NADPH-dependent reductase KanK. Angew. Chem. Int. Ed. Engl. 51 (2012) 3428-3431. [PMID: 22374809]

EC 1.14.11.38

Accepted name: verruculogen synthase

Reaction: fumitremorgin B + 2-oxoglutarate + 2 O₂ + reduced acceptor = verruculogen + succinate + CO₂ + H₂O + acceptor

For diagram of reaction click here.

Glossary: fumitremorgin B = (5aR,6S,12S,14aS)-5a,6-dihydroxy-9-methoxy-11-(3-methylbut-2-en-1-yl)-12-(2-methylprop-1-en-1-yl)-1,2,3,5a,6,11,12,14a-octahydro-5H,14H-pyrrolo[1'',2'':4',5']pyrazino[1',2':1,6]pyrido[3,4-b]indole-5,14-dione
verruculogen = (5R,10S,10aR,14aS,15bS)-10,10a-dihydroxy-6-methoxy-2,2-dimethyl-5-(2-methylprop-1-en-1-yl)-1,10,10a,14,14a,15b-hexahydro-12H-3,4-dioxa-5a,11a,15a-triazacycloocta[1,2,3-lm]indeno[5,6-b]fluorene-11,15(2H,13H)-dione

Other name(s): fmtF (gene name); FmtOx1

Systematic name: fumitremorgin B,2-oxoglutarate:oxygen oxidoreductase (verruculogen-forming)

Comments: Requires Fe²⁺ and ascorbate. Found in the fungus Aspergillus fumigatus. Both atoms of a dioxygen molecule are incorporated into verruculogen [1,2]. Involved in the biosynthetic pathways of several indole alkaloids such as fumitremorgin A.

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

References:

1. Steffan, N., Grundmann, A., Afiyatullov, S., Ruan, H. and Li, S.M. FtmOx1, a non-heme Fe(II) and α-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus. Org. Biomol. Chem. 7 (2009) 4082-4087. [PMID: 19763315]

2. Kato, N., Suzuki, H., Takagi, H., Uramoto, M., Takahashi, S. and Osada, H. Gene disruption and biochemical characterization of verruculogen synthase of Aspergillus fumigatus. ChemBioChem. 12 (2011) 711-714. [PMID: 21404415]

EC 1.14.11.39

Accepted name: L-asparagine hydroxylase

Reaction: L-asparagine + 2-oxoglutarate + O₂ = (2S,3S)-3-hydroxyasparagine + succinate + CO₂

Other name(s): L-asparagine 3-hydroxylase; AsnO

Systematic name: L-asparagine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires Fe²⁺. The enzyme is only able to hydroxylate free L-asparagine. It is not active toward D-asparagine. The β-hydroxylated asparagine produced is incorporated at position 9 of the calcium-dependent antibiotic (CDA), an 11-residue non-ribosomally synthesized acidic lipopeptide lactone.

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

References:

1. Strieker, M., Kopp, F., Mahlert, C., Essen, L.O. and Marahiel, M.A. Mechanistic and structural basis of stereospecific Cβ-hydroxylation in calcium-dependent antibiotic, a daptomycin-type lipopeptide. ACS Chem. Biol. 2 (2007) 187-196. [PMID: 17373765]

EC 1.14.11.40

Accepted name: enduracididine β-hydroxylase

Reaction: L-enduracididine + 2-oxoglutarate + O₂ = (3S)-3-hydroxy-L-enduracididine + succinate + CO₂

Glossary: L-enduracididine = 3-[(4R)-2-iminoimidazolidin-4-yl]-L-alanine = 2-amino-3-[(2S)-iminoimidazolin-4-yl]propanoic acid
(3S)-3-hydroxy-L-enduracididine = (2S,3R)-2-amino-3-hydroxy-3-[(S)-2-iminoimidazolidin-4-yl]propanoic acid = (3R)-3-[(4S)-2-iminoimidazolidin-4-yl]-L-serine

Other name(s): MppO; L-enduracididine,2-oxoglutarate:O₂ oxidoreductase (3-hydroxylating)

Systematic name: L-enduracididine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Fe²⁺-dependent enzyme. The enzyme is involved in biosynthesis of the nonproteinogenic amino acid β-hydroxyenduracididine, a component of the mannopeptimycins (cyclic glycopeptide antibiotic), produced by Streptomyces hygroscopicus NRRL 30439.

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

References:

1. Haltli, B., Tan, Y., Magarvey, N.A., Wagenaar, M., Yin, X., Greenstein, M., Hucul, J.A. and Zabriskie, T.M. Investigating β-hydroxyenduracididine formation in the biosynthesis of the mannopeptimycins. Chem. Biol. 12 (2005) 1163-1168. [PMID: 16298295]

2. Magarvey, N.A., Haltli, B., He, M., Greenstein, M. and Hucul, J.A. Biosynthetic pathway for mannopeptimycins, lipoglycopeptide antibiotics active against drug-resistant gram-positive pathogens. Antimicrob. Agents Chemother. 50 (2006) 2167-2177. [PMID: 16723579]

EC 1.14.11.41

Accepted name: L-arginine hydroxylase

Reaction: L-arginine + 2-oxoglutarate + O₂ = (3S)-3-hydroxy-L-arginine + succinate + CO₂

Other name(s): VioC (ambiguous); L-arginine,2-oxoglutarate:O₂ oxidoreductase (3-hydroxylating)

Systematic name: L-arginine,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Fe²⁺-dependent enzyme. The enzyme is involved in the biosynthesis of the cyclic pentapeptide antibiotic viomycin. It differs from EC 1.14.20.7, 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming), because it does not form guanidine and (S)-1-pyrroline-5-carboxylate from 3-hydroxy-L-arginine.

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

References:

1. Ju, J., Ozanick, S.G., Shen, B. and Thomas, M.G. Conversion of (2S)-arginine to (2S,3R)-capreomycidine by VioC and VioD from the viomycin biosynthetic pathway of Streptomyces sp. strain ATCC11861. ChemBioChem. 5 (2004) 1281-1285. [PMID: 15368582]

2. Helmetag, V., Samel, S.A., Thomas, M.G., Marahiel, M.A. and Essen, L.O. Structural basis for the erythro-stereospecificity of the L-arginine oxygenase VioC in viomycin biosynthesis. FEBS J. 276 (2009) 3669-3682. [PMID: 19490124]

EC 1.14.11.42

Accepted name: tRNA^Phe (7-(3-amino-3-carboxypropyl)wyosine³⁷-C²)-hydroxylase

Reaction: 7-(3-amino-3-carboxypropyl)wyosine³⁷ in tRNA^Phe + 2-oxoglutarate + O₂ = 7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine³⁷ in tRNA^Phe + succinate + CO₂

For diagram of reaction click here.

Glossary: 7-(3-amino-3-carboxypropyl)wyosine = 7-[(3S)-3-amino-3-carboxypropyl]-4,6-dimethyl-3-(-D-ribofuranosyl)-3,4-dihydro-9H-imidazo[1,2-a]purin-9-one
7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine = 4-[4,6-dimethyl-9-oxo-3-(-D-ribofuranosyl)-4,9-dihydro-3H-imidazo[1,2-a]purin-7-yl]-L-threonine

Other name(s): TYW5; tRNA yW-synthesizing enzyme 5

Systematic name: tRNA^Phe 7-(3-amino-3-carboxypropyl)wyosine³⁷,2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating)

Comments: Requires Fe²⁺. The enzyme is not active with wybutosine.

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

References:

1. Noma, A., Ishitani, R., Kato, M., Nagao, A., Nureki, O. and Suzuki, T. Expanding role of the jumonji C domain as an RNA hydroxylase. J. Biol. Chem. 285 (2010) 34503-34507. [PMID: 20739293]

2. Kato, M., Araiso, Y., Noma, A., Nagao, A., Suzuki, T., Ishitani, R. and Nureki, O. Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification. Nucleic Acids Res. 39 (2011) 1576-1585. [PMID: 20972222]

EC 1.14.11.43

Accepted name: (S)-dichlorprop dioxygenase (2-oxoglutarate)

Reaction: (1) (S)-2-(4-chloro-2-methylphenoxy)propanoate + 2-oxoglutarate + O₂ = 4-chloro-2-methylphenol + pyruvate + succinate + CO₂
(2) (S)-(2,4-dichlorophenoxy)propanoate + 2-oxoglutarate + O₂ = 2,4-dichlorophenol + pyruvate + succinate + CO₂

Glossary: (S)-2-(4-chloro-2-methylphenoxy)propanoate = (S)-mecoprop
(S)-(2,4-dichlorophenoxy)propanoate = (S)-dichlorprop

Other name(s): SdpA; α-ketoglutarate-dependent (S)-dichlorprop dioxygenase; (S)-phenoxypropionate/α-ketoglutarate-dioxygenase; 2-oxoglutarate-dependent (S)-dichlorprop dioxygenase; (S)-mecoprop dioxygenase; 2-oxoglutarate-dependent (S)-mecoprop dioxygenase

Systematic name: (S)-2-(4-chloro-2-methylphenoxy)propanoate,2-oxoglutarate:oxygen oxidoreductase (pyruvate-forming)

Comments: Fe²⁺-dependent enzyme. The enzymes from the Gram-negative bacteria Delftia acidovorans MC1 and Sphingomonas herbicidovorans MH are involved in the degradation of the (S)-enantiomer of the phenoxyalkanoic acid herbicides mecoprop and dichlorprop [1,2].

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

References:

1. Westendorf, A., Benndorf, D., Muller, R.H. and Babel, W. The two enantiospecific dichlorprop/α-ketoglutarate-dioxygenases from Delftia acidovorans MC1 - protein and sequence data of RdpA and SdpA. Microbiol. Res. 157 (2002) 317-322. [PMID: 12501996]

2. Muller, T.A., Fleischmann, T., van der Meer, J.R. and Kohler, H.P. Purification and characterization of two enantioselective α-ketoglutarate-dependent dioxygenases, RdpA and SdpA, from Sphingomonas herbicidovorans MH. Appl. Environ. Microbiol. 72 (2006) 4853-4861. [PMID: 16820480]

3. Muller, T.A., Zavodszky, M.I., Feig, M., Kuhn, L.A. and Hausinger, R.P. Structural basis for the enantiospecificities of R- and S-specific phenoxypropionate/α-ketoglutarate dioxygenases. Protein Sci. 15 (2006) 1356-1368. [PMID: 16731970]

EC 1.14.11.44

Accepted name: (R)-dichlorprop dioxygenase (2-oxoglutarate)

Reaction: (1) (R)-2-(4-chloro-2-methylphenoxy)propanoate + 2-oxoglutarate + O₂ = 4-chloro-2-methylphenol + pyruvate + succinate + CO₂
(2) (R)-(2,4-dichlorophenoxy)propanoate + 2-oxoglutarate + O₂ = 2,4-dichlorophenol + pyruvate + succinate + CO₂

Glossary: (R)-2-(4-chloro-2-methylphenoxy)propanoate = (R)-mecoprop
(R)-(2,4-dichlorophenoxy)propanoate = (R)-dichlorprop

Other name(s): RdpA; α-ketoglutarate-dependent (R)-dichlorprop dioxygenase; (R)-phenoxypropionate/α-ketoglutarate-dioxygenase; 2-oxoglutarate-dependent (R)-dichlorprop dioxygenase; (R)-mecoprop dioxygenase; 2-oxoglutarate-dependent (R)-mecoprop dioxygenase

Systematic name: (R)-2-(4-chloro-2-methylphenoxy)propanoate,2-oxoglutarate:oxygen oxidoreductase (pyruvate-forming)

Comments: Fe²⁺-dependent enzyme. The enzymes from the Gram-negative bacteria Delftia acidovorans MC1 and Sphingomonas herbicidovorans MH are involved in the degradation of the (R)-enantiomer of the phenoxyalkanoic acid herbicides mecoprop and dichlorprop [1,2].

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

References:

1. Westendorf, A., Benndorf, D., Muller, R.H. and Babel, W. The two enantiospecific dichlorprop/α-ketoglutarate-dioxygenases from Delftia acidovorans MC1 - protein and sequence data of RdpA and SdpA. Microbiol. Res. 157 (2002) 317-322. [PMID: 12501996]

2. Muller, T.A., Fleischmann, T., van der Meer, J.R. and Kohler, H.P. Purification and characterization of two enantioselective α-ketoglutarate-dependent dioxygenases, RdpA and SdpA, from Sphingomonas herbicidovorans MH. Appl. Environ. Microbiol. 72 (2006) 4853-4861. [PMID: 16820480]

3. Muller, T.A., Zavodszky, M.I., Feig, M., Kuhn, L.A. and Hausinger, R.P. Structural basis for the enantiospecificities of R- and S-specific phenoxypropionate/α-ketoglutarate dioxygenases. Protein Sci. 15 (2006) 1356-1368. [PMID: 16731970]

EC 1.14.11.45

Accepted name: L-isoleucine 4-hydroxylase

Reaction: L-isoleucine + 2-oxoglutarate + O₂ = (4S)-4-hydroxy-L-isoleucine + succinate + CO₂

Glossary: (4S)-4-hydroxy-L-isoleucine = (2S,3R,4S)-2-amino-4-hydroxy-3-methylpentanoate

Other name(s): ido (gene name)

Systematic name: L-isoleucine,2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)

Comments: The enzyme, characterized from the bacterium Bacillus thuringiensis, can also catalyse the hydroxylation of L-leucine, L-norvaline, L-norleucine, and L-allo-isoleucine, as well as the sulfoxidation of L-methionine, L-ethionine, S-methyl-L-cysteine, S-ethyl-L-cysteine, and S-allyl-L-cysteine.

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

References:

1. Kodera, T., Smirnov, S.V., Samsonova, N.N., Kozlov, Y.I., Koyama, R., Hibi, M., Ogawa, J., Yokozeki, K. and Shimizu, S. A novel L-isoleucine hydroxylating enzyme, L-isoleucine dioxygenase from Bacillus thuringiensis, produces (2S,3R,4S)-4-hydroxyisoleucine. Biochem. Biophys. Res. Commun. 390 (2009) 506-510. [PMID: 19850012]

2. Hibi, M., Kawashima, T., Kodera, T., Smirnov, S.V., Sokolov, P.M., Sugiyama, M., Shimizu, S., Yokozeki, K. and Ogawa, J. Characterization of Bacillus thuringiensis-L-isoleucine dioxygenase for production of useful amino acids. Appl. Environ. Microbiol. 77 (2011) 6926-6930. [PMID: 21821743]

3. Hibi, M., Kawashima, T., Yajima, H., Smirnov, S.V., Kodera, T., Sugiyama, M., Shimizu, S., Yokozeki, K., and Ogawa, J. Enzymatic synthesis of chiral amino acid sulfoxides by Fe(II)/α ketoglutarate-dependent dioxygenase. Tetrahedron Asym 24 (2013) 990-994.

EC 1.14.11.46

Accepted name: 2-aminoethylphosphonate dioxygenase

Reaction: (2-aminoethyl)phosphonate + 2-oxoglutarate + O₂ = (2-amino-1-hydroxyethyl)phosphonate + succinate + CO₂

Other name(s): phnY (gene name)

Systematic name: (2-aminoethyl)phosphonate,2-oxoglutarate:oxygen oxidoreductase (1-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme, characterized from an uncultured marine bacterium, is involved in a (2-aminoethyl)phosphonate degradation pathway.

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

References:

1. McSorley, F.R., Wyatt, P.B., Martinez, A., DeLong, E.F., Hove-Jensen, B. and Zechel, D.L. PhnY and PhnZ comprise a new oxidative pathway for enzymatic cleavage of a carbon-phosphorus bond. J. Am. Chem. Soc. 134 (2012) 8364-8367. [PMID: 22564006]

EC 1.14.11.47

Accepted name: [50S ribosomal protein L16]-arginine 3-hydroxylase

Reaction: [50S ribosomal protein L16]-L-Arg⁸¹ + 2-oxoglutarate + O₂ = [50S ribosomal protein L16]-(3R)-3-hydroxy-L-Arg⁸¹ + succinate + CO₂

Other name(s): ycfD (gene name)

Systematic name: [50S ribosomal protein L16]-L-Arg⁸¹,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)

Comments: The enzyme, characterized from the bacterium Escherichia coli, hydroxylates an arginine residue on the 50S ribosomal protein L16, and is involved in regulation of bacterial ribosome assembly.

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

References:

1. Ge, W., Wolf, A., Feng, T., Ho, C.H., Sekirnik, R., Zayer, A., Granatino, N., Cockman, M.E., Loenarz, C., Loik, N.D., Hardy, A.P., Claridge, T.D., Hamed, R.B., Chowdhury, R., Gong, L., Robinson, C.V., Trudgian, D.C., Jiang, M., Mackeen, M.M., McCullagh, J.S., Gordiyenko, Y., Thalhammer, A., Yamamoto, A., Yang, M., Liu-Yi, P., Zhang, Z., Schmidt-Zachmann, M., Kessler, B.M., Ratcliffe, P.J., Preston, G.M., Coleman, M.L. and Schofield, C.J. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans. Nat. Chem. Biol. 8 (2012) 960-962. [PMID: 23103944]

2. van Staalduinen, L.M., Novakowski, S.K. and Jia, Z. Structure and functional analysis of YcfD, a novel 2-oxoglutarate/Fe²(+)-dependent oxygenase involved in translational regulation in Escherichia coli. J. Mol. Biol. 426 (2014) 1898-1910. [PMID: 24530688]

EC 1.14.11.48

Accepted name: xanthine dioxygenase

Reaction: xanthine + 2-oxoglutarate + O₂ = urate + succinate + CO₂

For diagram click here.

Other name(s): XanA; α-ketoglutarate-dependent xanthine hydroxylase

Systematic name: xanthine,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires Fe²⁺ and L-ascorbate. The enzyme, which was characterized from fungi, is specific for xanthine.

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

References:

1. Cultrone, A., Scazzocchio, C., Rochet, M., Montero-Moran, G., Drevet, C. and Fernandez-Martin, R. Convergent evolution of hydroxylation mechanisms in the fungal kingdom: molybdenum cofactor-independent hydroxylation of xanthine via α-ketoglutarate-dependent dioxygenases. Mol. Microbiol. 57 (2005) 276-290. [PMID: 15948966]

2. Montero-Moran, G.M., Li, M., Rendon-Huerta, E., Jourdan, F., Lowe, D.J., Stumpff-Kane, A.W., Feig, M., Scazzocchio, C. and Hausinger, R.P. Purification and characterization of the Fe^II- and α-ketoglutarate-dependent xanthine hydroxylase from Aspergillus nidulans. Biochemistry 46 (2007) 5293-5304. [PMID: 17429948]

3. Li, M., Muller, T.A., Fraser, B.A. and Hausinger, R.P. Characterization of active site variants of xanthine hydroxylase from Aspergillus nidulans. Arch. Biochem. Biophys. 470 (2008) 44-53. [PMID: 18036331]

EC 1.14.11.49

Accepted name: uridine-5'-phosphate dioxygenase

Reaction: UMP + 2-oxoglutarate + O₂ = 5'-dehydrouridine + succinate + CO₂ + phosphate

For diagram of reaction click here.

Glossary: 5'-dehydrouridine = uridine-5'-aldehyde

Other name(s): lipL (gene name)

Systematic name: UMP,2-oxoglutarate:oxygen oxidoreductase

Comments: The enzyme catalyses a net dephosphorylation and oxidation of UMP to generate 5'-dehydrouridine, the first intermediate in the biosynthesis of the unusual aminoribosyl moiety found in several C⁷-furanosyl nucleosides such as A-90289s, caprazamycins, liposidomycins, muraymycins and FR-900453. Requires Fe²⁺.

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

References:

1. Yang, Z., Chi, X., Funabashi, M., Baba, S., Nonaka, K., Pahari, P., Unrine, J., Jacobsen, J.M., Elliott, G.I., Rohr, J. and Van Lanen, S.G. Characterization of LipL as a non-heme, Fe(II)-dependent α-ketoglutarate:UMP dioxygenase that generates uridine-5'-aldehyde during A-90289 biosynthesis. J. Biol. Chem. 286 (2011) 7885-7892. [PMID: 21216959]

2. Yang, Z., Unrine, J., Nonaka, K. and Van Lanen, S.G. Fe(II)-dependent, uridine-5'-monophosphate α-ketoglutarate dioxygenases in the synthesis of 5'-modified nucleosides. Methods Enzymol. 516 (2012) 153-168. [PMID: 23034228]

[EC 1.14.11.50 Transferred entry: (–)-deoxypodophyllotoxin synthase. Now EC 1.14.20.8, (–)-deoxypodophyllotoxin synthase (EC 1.14.11.50 created 2016, deleted 2018)]

EC 1.14.11.51

Accepted name: DNA N⁶-methyladenine demethylase

Reaction: N⁶-methyladenine in DNA + 2-oxoglutarate + O₂ = adenine in DNA + formaldehyde + succinate + CO₂

Other name(s): ALKBH1

Systematic name: DNA-N⁶-methyladenosine,2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)

Comments: Contains iron(II). Catalyses oxidative demethylation of DNA N⁶-methyladenine, a prevalent modification in LINE-1 transposons, which are specifically enriched on the human X chromosome.

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

References:

1. Wu, T.P., Wang, T., Seetin, M.G., Lai, Y., Zhu, S., Lin, K., Liu, Y., Byrum, S.D., Mackintosh, S.G., Zhong, M., Tackett, A., Wang, G., Hon, L.S., Fang, G., Swenberg, J.A. and Xiao, A.Z. DNA methylation on N-adenine in mammalian embryonic stem cells. Nature 532 (2016) 329-333. [PMID: 27027282]

EC 1.14.11.52

Accepted name: validamycin A dioxygenase

Reaction: validamycin A + 2-oxoglutarate + O₂ = validamycin B + succinate + CO₂

For diagram of reaction click here.

Glossary: validamycin A = (1R,2R,3S,4S,6R)-2,3-dihydroxy-6-(hydroxymethyl)-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}cyclohexyl β-D-glucopyranoside
validamycin B = (1R,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-6-(hydroxymethyl)-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}cyclohexyl β-D-glucopyranoside

Other name(s): vldW (gene name)

Systematic name: validamycin-A,2-oxoglutarate:oxygen oxidoreductase (6'-hydroxylating)

Comments: The enzyme was characterized from the bacterium Streptomyces hygroscopicus subsp. limoneus. Requires Fe²⁺.

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

References:

1. Almabruk, K.H., Asamizu, S., Chang, A., Varghese, S.G. and Mahmud, T. The α-ketoglutarate/Fe(II)-dependent dioxygenase VldW is responsible for the formation of validamycin B. Chembiochem 13 (2012) 2209-2211. [PMID: 22961651]

EC 1.14.11.53

Accepted name: mRNA N⁶-methyladenine demethylase

Reaction: N⁶-methyladenine in mRNA + 2-oxoglutarate + O₂ = adenine in mRNA + formaldehyde + succinate + CO₂

Other name(s): ALKBH5; FTO

Systematic name: mRNA-N⁶-methyladenosine,2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)

Comments: Contains iron(II). Catalyses oxidative demethylation of mRNA N⁶-methyladenine. The FTO enzyme from human can also demethylate N³-methylthymine from single stranded DNA and N³-methyluridine from single stranded RNA [1,2] with low activity [3].

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

References:

1. Jia, G., Yang, C.G., Yang, S., Jian, X., Yi, C., Zhou, Z. and He, C. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 582 (2008) 3313-3319. [PMID: 18775698]

2. Han, Z., Niu, T., Chang, J., Lei, X., Zhao, M., Wang, Q., Cheng, W., Wang, J., Feng, Y. and Chai, J. Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464 (2010) 1205-1209. [PMID: 20376003]

3. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.G. and He, C. N⁶-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7 (2011) 885-887. [PMID: 22002720]

4. Zheng, G., Dahl, J.A., Niu, Y., Fedorcsak, P., Huang, C.M., Li, C.J., Vagbo, C.B., Shi, Y., Wang, W.L., Song, S.H., Lu, Z., Bosmans, R.P., Dai, Q., Hao, Y.J., Yang, X., Zhao, W.M., Tong, W.M., Wang, X.J., Bogdan, F., Furu, K., Fu, Y., Jia, G., Zhao, X., Liu, J., Krokan, H.E., Klungland, A., Yang, Y.G. and He, C. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49 (2013) 18-29. [PMID: 23177736]

5. Feng, C., Liu, Y., Wang, G., Deng, Z., Zhang, Q., Wu, W., Tong, Y., Cheng, C. and Chen, Z. Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition. J. Biol. Chem. 289 (2014) 11571-11583. [PMID: 24616105]

6. Xu, C., Liu, K., Tempel, W., Demetriades, M., Aik, W., Schofield, C.J. and Min, J. Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N⁶-methyladenosine RNA demethylation. J. Biol. Chem. 289 (2014) 17299-17311. [PMID: 24778178]

7. Aik, W., Scotti, J.S., Choi, H., Gong, L., Demetriades, M., Schofield, C.J. and McDonough, M.A. Structure of human RNA N⁶-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation. Nucleic Acids Res. 42 (2014) 4741-4754. [PMID: 24489119]

EC 1.14.11.54

Accepted name: mRNA N¹-methyladenine demethylase

Reaction: N¹-methyladenine in mRNA + 2-oxoglutarate + O₂ = adenine in mRNA + formaldehyde + succinate + CO₂

Other name(s): ALKBH3

Systematic name: mRNA-N¹-methyladenine,2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)

Comments: Contains iron(II). Catalyses oxidative demethylation of mRNA N¹-methyladenine. The enzyme is also involved in alkylation repair in DNA [2].

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

References:

1. Sundheim, O., Vågbø, C.B., Bjørås, M., Sousa, M.M., Talstad, V., Aas, P.A., Drabløs, F., Krokan, H.E., Tainer, J.A. and Slupphaug, G. Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage. EMBO J. 25 (2006) 3389-3397. [PMID: 16858410]

2. Dango, S., Mosammaparast, N., Sowa, M.E., Xiong, L.J., Wu, F., Park, K., Rubin, M., Gygi, S., Harper, J.W. and Shi, Y. DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Mol. Cell 44 (2011) 373-384. [PMID: 22055184]

3. Li, X., Xiong, X., Wang, K., Wang, L., Shu, X., Ma, S. and Yi, C. Transcriptome-wide mapping reveals reversible and dynamic N-methyladenosine methylome. Nat. Chem. Biol. (2016) . [PMID: 26863410]

EC 1.14.11.55

Accepted name: ectoine hydroxylase

Reaction: ectoine + 2-oxoglutarate + O₂ = 5-hydroxyectoine + succinate + CO₂

Glossary: ectoine = (4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylate
5-hydroxyectoine = (4S,5S)-5-hydroxy-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylate

Other name(s): ectD (gene name); ectoine dioxygenase

Systematic name: ectoine,2-oxoglutarate:oxygen oxidoreductase (5-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme, found in bacteria, is specific for ectoine.

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

References:

1. Bursy, J., Pierik, A.J., Pica, N. and Bremer, E. Osmotically induced synthesis of the compatible solute hydroxyectoine is mediated by an evolutionarily conserved ectoine hydroxylase. J. Biol. Chem. 282 (2007) 31147-31155. [PMID: 17636255]

2. Bursy, J., Kuhlmann, A.U., Pittelkow, M., Hartmann, H., Jebbar, M., Pierik, A.J. and Bremer, E. Synthesis and uptake of the compatible solutes ectoine and 5-hydroxyectoine by Streptomyces coelicolor A3(2) in response to salt and heat stresses. Appl. Environ. Microbiol. 74 (2008) 7286-7296. [PMID: 18849444]

3. Reuter, K., Pittelkow, M., Bursy, J., Heine, A., Craan, T. and Bremer, E. Synthesis of 5-hydroxyectoine from ectoine: crystal structure of the non-heme iron(II) and 2-oxoglutarate-dependent dioxygenase EctD. PLoS One 5 (2010) e10647. [PMID: 20498719]

EC 1.14.11.56

Accepted name: L-proline cis-4-hydroxylase

Reaction: L-proline + 2-oxoglutarate + O₂ = cis-4-hydroxy-L-proline + succinate + CO₂

Systematic name: L-proline,2-oxoglutarate:oxygen oxidoreductase (cis-4-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme, isolated from Rhizobium species, only produces cis-4-hydroxy-L-proline (cf. EC 1.14.11.57, L-proline trans-4-hydroxylase).

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

References:

1. Hara, R. and Kino, K. Characterization of novel 2-oxoglutarate dependent dioxygenases converting L-proline to cis-4-hydroxy-L-proline. Biochem. Biophys. Res. Commun. 379 (2009) 882-886. [PMID: 19133227]

EC 1.14.11.57

Accepted name: L-proline trans-4-hydroxylase

Reaction: L-proline + 2-oxoglutarate + O₂ = trans-4-hydroxy-L-proline + succinate + CO₂

Systematic name: L-proline,2-oxoglutarate:oxygen oxidoreductase (trans-4-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme, isolated from multiple bacterial species, only produces trans-4-hydroxy-L-proline (cf. EC 1.14.11.56, L-proline cis-4-hydroxylase).

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

References:

1. Lawrence, C.C., Sobey, W.J., Field, R.A., Baldwin, J.E. and Schofield, C.J. Purification and initial characterization of proline 4-hydroxylase from Streptomyces griseoviridus P8648: a 2-oxoacid, ferrous-dependent dioxygenase involved in etamycin biosynthesis. Biochem. J. 313 (1996) 185-191. [PMID: 8546682]

2. Shibasaki, T., Mori, H., Chiba, S. and Ozaki, A. Microbial proline 4-hydroxylase screening and gene cloning. Appl. Environ. Microbiol. 65 (1999) 4028-4031. [PMID: 10473412]

EC 1.14.11.58

Accepted name: ornithine lipid ester-linked acyl 2-hydroxylase

Reaction: an ornithine lipid + 2-oxoglutarate + O₂ = a 2-hydroxyornithine lipid + succinate + CO₂

Glossary: an ornithine lipid = an N^α-[(3R)-3-(acyloxy)acyl]-L-ornithine
a 2-hydroxyornithine lipid = an N^α-[(3R)-3-(2-hydroxyacyloxy)acyl]-L-ornithine

Other name(s): olsC (gene name)

Systematic name: ornithine lipid,2-oxoglutarate:oxygen oxidoreductase (ester-linked acyl 2-hydroxylase)

Comments: The enzyme, characterized from the bacterium Rhizobium tropici, catalyses the hydroxylation of C-2 of the fatty acyl group that is ester-linked to the 3-hydroxy position of the amide-linked fatty acid.

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

References:

1. Rojas-Jimenez, K., Sohlenkamp, C., Geiger, O., Martinez-Romero, E., Werner, D. and Vinuesa, P. A ClC chloride channel homolog and ornithine-containing membrane lipids of Rhizobium tropici CIAT899 are involved in symbiotic efficiency and acid tolerance. Mol Plant Microbe Interact 18 (2005) 1175-1185. [PMID: 16353552]

2. Vences-Guzman, M.A., Guan, Z., Ormeno-Orrillo, E., Gonzalez-Silva, N., Lopez-Lara, I.M., Martinez-Romero, E., Geiger, O. and Sohlenkamp, C. Hydroxylated ornithine lipids increase stress tolerance in Rhizobium tropici CIAT899. Mol. Microbiol. 79 (2011) 1496-1514. [PMID: 21205018]

EC 1.14.11.59

Accepted name: 2,4-dihydroxy-1,4-benzoxazin-3-one-glucoside dioxygenase

Reaction: (2R)-4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside + 2-oxoglutarate + O₂ = (2R)-4,7-dihydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside + succinate + CO₂ + H₂O

For diagram of reaction click here.

Glossary: (2R)-4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside = DIBOA β-D-glucoside
(2R)-4,7-dihydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside = TRIBOA β-D-glucoside

Other name(s): BX6 (gene name); DIBOA-Glc dioxygenase

Systematic name: (2R)-4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside:oxygen oxidoreductase (7-hydroxylating)

Comments: The enzyme is involved in the biosynthesis of protective and allelophatic benzoxazinoids in some plants, most commonly from the family of Poaceae (grasses).

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

References:

1. Jonczyk, R., Schmidt, H., Osterrieder, A., Fiesselmann, A., Schullehner, K., Haslbeck, M., Sicker, D., Hofmann, D., Yalpani, N., Simmons, C., Frey, M. and Gierl, A. Elucidation of the final reactions of DIMBOA-glucoside biosynthesis in maize: characterization of Bx6 and Bx7. Plant Physiol. 146 (2008) 1053-1063. [PMID: 18192444]

EC 1.14.11.60

Accepted name: scopoletin 8-hydroxylase

Reaction: scopoletin + 2-oxoglutarate + O₂ = fraxetin + succinate + CO₂

Glossary: fraxetin = 7,8-dihydroxy-6-methoxy-2H-chromen-2-one
scopoletin = 7-hydroxy-6-methoxy-2H-chromen-2-one

Other name(s): S8H (gene name)

Systematic name: scopoletin,2-oxoglutarate:oxygen oxidoreductase (8-hydroxylating)

Comments: Requires iron(II) and ascorbate. A protein involved in biosynthesis of iron(III)-chelating coumarins in higher plants.

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

References:

1. Siwinska, J., Siatkowska, K., Olry, A., Grosjean, J., Hehn, A., Bourgaud, F., Meharg, A.A., Carey, M., Lojkowska, E. and Ihnatowicz, A. Scopoletin 8-hydroxylase: a novel enzyme involved in coumarin biosynthesis and iron-deficiency responses in Arabidopsis. J. Exp. Bot. 69 (2018) 1735-1748. [PMID: 29361149]

2. Rajniak, J., Giehl, R.FH., Chang, E., Murgia, I., von Wiren, N. and Sattely, E.S. Biosynthesis of redox-active metabolites in response to iron deficiency in plants. Nat. Chem. Biol. 14 (2018) 442-450. [PMID: 29581584]

EC 1.14.11.61

Accepted name: feruloyl-CoA 6-hydroxylase

Reaction: trans-feruloyl-CoA + 2-oxoglutarate + O₂ = trans-6-hydroxyferuloyl-CoA + succinate + CO₂

Glossary: trans-feruloyl-CoA = 4-hydroxy-3-methoxycinnamoyl-CoA = (E)-3-(4-hydroxy-3-methoxyphenyl)propenoyl-CoA

Systematic name: feruloyl-CoA,2-oxoglutarate:oxygen oxidoreductase (6-hydroxylating)

Comments: Requires iron(II) and ascorbate. The product spontaneously undergoes trans-cis isomerization and lactonization to form scopoletin, liberating CoA in the process. The enzymes from the plants Ruta graveolens and Ipomoea batatas also act on trans-4-coumaroyl-CoA. cf. EC 1.14.11.62, trans-4-coumaroyl-CoA 2-hydroxylase.

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

References:

1. Kai, K., Mizutani, M., Kawamura, N., Yamamoto, R., Tamai, M., Yamaguchi, H., Sakata, K. and Shimizu, B. Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana. Plant J. 55 (2008) 989-999. [PMID: 18547395]

2. Bayoumi, S.A., Rowan, M.G., Blagbrough, I.S. and Beeching, J.R. Biosynthesis of scopoletin and scopolin in cassava roots during post-harvest physiological deterioration: the E-Z-isomerisation stage. Phytochemistry 69 (2008) 2928-2936. [PMID: 19004461]

3. Vialart, G., Hehn, A., Olry, A., Ito, K., Krieger, C., Larbat, R., Paris, C., Shimizu, B., Sugimoto, Y., Mizutani, M. and Bourgaud, F. A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2'-hydroxylase activity (C2’H): a missing step in the synthesis of umbelliferone in plants. Plant J. 70 (2012) 460-470. [PMID: 22168819]

4. Matsumoto, S., Mizutani, M., Sakata, K. and Shimizu, B. Molecular cloning and functional analysis of the ortho-hydroxylases of p-coumaroyl coenzyme A/feruloyl coenzyme A involved in formation of umbelliferone and scopoletin in sweet potato, Ipomoea batatas (L.) Lam. Phytochemistry 74 (2012) 49-57. [PMID: 22169019]

EC 1.14.11.62

Accepted name: trans-4-coumaroyl-CoA 2-hydroxylase

Reaction: trans-4-coumaroyl-CoA + 2-oxoglutarate + O₂ = 2,4-dihydroxycinnamoyl-CoA + succinate + CO₂

For diagram of reaction click here

Glossary: trans-4-coumaroyl-CoA = (2E)-3-(4-hydroxyphenyl)prop-2-enoyl-CoA
2,4-dihydroxycinnamoyl-CoA = (2E)-3-(2,4-dihydroxyphenyl)prop-2-enoyl-CoA
umbelliferone = 7-hydroxycoumarin

Other name(s): Diox4 (gene name); C2'H (gene name)

Systematic name: (2E)-3-(4-hydroxyphenyl)prop-2-enoyl-CoA,2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating)

Comments: Requires iron(II) and ascorbate. The product spontaneously undergoes trans-cis isomerization followed by lactonization and cyclization, liberating CoA and forming umbelliferone. The enzymes from the plants Ruta graveolens and Ipomoea batatas also act on trans-feruloyl-CoA (cf. EC 1.14.11.61, feruloyl-CoA 6-hydroxylase).

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

References:

1. Vialart, G., Hehn, A., Olry, A., Ito, K., Krieger, C., Larbat, R., Paris, C., Shimizu, B., Sugimoto, Y., Mizutani, M. and Bourgaud, F. A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2'-hydroxylase activity (C2'H): a missing step in the synthesis of umbelliferone in plants. Plant J. 70 (2012) 460-470. [PMID: 22168819]

2. Matsumoto, S., Mizutani, M., Sakata, K. and Shimizu, B. Molecular cloning and functional analysis of the ortho-hydroxylases of p-coumaroyl coenzyme A/feruloyl coenzyme A involved in formation of umbelliferone and scopoletin in sweet potato, Ipomoea batatas (L.) Lam. Phytochemistry 74 (2012) 49-57. [PMID: 22169019]

EC 1.14.11.63

Accepted name: peptidyl-lysine (3S)-dioxygenase

Reaction: a [protein]-L-lysine + 2-oxoglutarate + O₂ = a [protein]-(3S)-3-hydroxy-L-lysine + succinate + CO₂

Other name(s): JMJD7 (gene name); Jumonji domain-containing protein 7; JmjC domain-containing protein 7

Systematic name: [protein]-L-lysine,2-oxoglutarate:oxygen oxidoreductase (3S-hydroxylating)

Comments: Requires iron(II). The enzyme acts on specific lysine residues in its substrates, and is stereo-specific. The enzyme encoded by the human JMJD7 gene acts specifically on two related members of the translation factor family of GTPases, DRG1 and DRG2.

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

References:

1. Markolovic, S., Zhuang, Q., Wilkins, S.E., Eaton, C.D., Abboud, M.I., Katz, M.J., McNeil, H.E., Lesniak, R.K., Hall, C., Struwe, W.B., Konietzny, R., Davis, S., Yang, M., Ge, W., Benesch, J.LP., Kessler, B.M., Ratcliffe, P.J., Cockman, M.E., Fischer, R., Wappner, P., Chowdhury, R., Coleman, M.L. and Schofield, C.J. The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases. Nat. Chem. Biol. 14 (2018) 688-695. [PMID: 29915238]

EC 1.14.11.64

Accepted name: glutarate dioxygenase

Reaction: glutarate + 2-oxoglutarate + O₂ = (S)-2-hydroxyglutarate + succinate + CO₂

Other name(s): csiD (gene name)

Systematic name: glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming)

Comments: Requires iron(II). The enzyme, characterized from the bacteria Escherichia coli and Pseudomonas putida, participates in L-lysine degradation in many bacteria. It provides an alternative route for L-glutarate degradation that does not proceed via CoA-activated intermediates.

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

References:

1. Knorr, S., Sinn, M., Galetskiy, D., Williams, R.M., Wang, C., Muller, N., Mayans, O., Schleheck, D. and Hartig, J.S. Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate. Nat Commun 9 (2018) 5071. [PMID: 30498244]

2. Zhang, M., Gao, C., Guo, X., Guo, S., Kang, Z., Xiao, D., Yan, J., Tao, F., Zhang, W., Dong, W., Liu, P., Yang, C., Ma, C. and Xu, P. Increased glutarate production by blocking the glutaryl-CoA dehydrogenation pathway and a catabolic pathway involving L-2-hydroxyglutarate. Nat Commun 9 (2018) 2114. [PMID: 29844506]

EC 1.14.11.65

Accepted name: [histone H3]-dimethyl-L-lysine⁹ demethylase

Reaction: a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ + 2 2-oxoglutarate + 2 O₂ = a [histone H3]-L-lysine⁹ + 2 succinate + 2 formaldehyde + 2 CO₂ (overall reaction)
(1a) a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶-methyl-L-lysine⁹ + succinate + formaldehyde + CO₂
(1b) a [histone H3]-N⁶-methyl-L-lysine⁹ + 2-oxoglutarate + O₂ = a [histone H3]-L-lysine⁹ + succinate + formaldehyde + CO₂

Other name(s): KDM3A (gene name); KDM3B (gene name); JMJD1A (gene name); JMJD1B (gene name); JHDM2A (gene name); JHDM2B (gene name); KDM7B (gene name); PHF8 (gene name); HR (gene name)

Systematic name: [histone H3]-N⁶,N⁶-dimethyl-L-lysine-9,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the di- and mono-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.66, [histone H3]-trimethyl-L-lysine⁹ demethylase.

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

References:

1. Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. JHDM2A, a JmjC-containing H₃K9 demethylase, facilitates transcription activation by androgen receptor. Cell 125 (2006) 483-495. [PMID: 16603237]

2. Loh, Y.H., Zhang, W., Chen, X., George, J. and Ng, H.H. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 21 (2007) 2545-2557. [PMID: 17938240]

3. Feng, W., Yonezawa, M., Ye, J., Jenuwein, T. and Grummt, I. PHF8 activates transcription of rRNA genes through H₃K4me3 binding and H₃K9me1/2 demethylation. Nat. Struct. Mol. Biol. 17 (2010) 445-450. [PMID: 20208542]

4. Kuroki, S., Matoba, S., Akiyoshi, M., Matsumura, Y., Miyachi, H., Mise, N., Abe, K., Ogura, A., Wilhelm, D., Koopman, P., Nozaki, M., Kanai, Y., Shinkai, Y. and Tachibana, M. Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a. Science 341 (2013) 1106-1109. [PMID: 24009392]

5. Liu, L., Kim, H., Casta, A., Kobayashi, Y., Shapiro, L.S. and Christiano, A.M. Hairless is a histone H3K9 demethylase. FASEB J. 28 (2014) 1534-1542. [PMID: 24334705]

EC 1.14.11.66

Accepted name: [histone H3]-trimethyl-L-lysine⁹ demethylase

Reaction: a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁹ + 2 2-oxoglutarate + 2 O₂ = a [histone H3]-N⁶-methyl-L-lysine⁹ + 2 succinate + 2 formaldehyde + 2 CO₂ (overall reaction)
(1a) a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁹ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ + succinate + formaldehyde + CO₂
(1b) a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁹ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶-methyl-L-lysine⁹ + succinate + formaldehyde + CO₂

Other name(s): KDM4A (gene name); KDM4B (gene name); KDM4C (gene name); KDM4D (gene name); JHDM3A (gene name); JMJD2 (gene name); JMJD2A (gene name); GASC1 (gene name)

Systematic name: [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine-9,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys⁹ residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.65, [histone H3]-dimethyl-L-lysine⁹ demethylase.

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

References:

1. Cloos, P.A., Christensen, J., Agger, K., Maiolica, A., Rappsilber, J., Antal, T., Hansen, K.H. and Helin, K. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 442 (2006) 307-311. [PMID: 16732293]

2. Fodor, B.D., Kubicek, S., Yonezawa, M., O'Sullivan, R.J., Sengupta, R., Perez-Burgos, L., Opravil, S., Mechtler, K., Schotta, G. and Jenuwein, T. Jmjd2b antagonizes H₃K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes Dev. 20 (2006) 1557-1562. [PMID: 16738407]

3. Klose, R.J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442 (2006) 312-316. [PMID: 16732292]

4. Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G., Colaiacovo, M. and Shi, Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125 (2006) 467-481. [PMID: 16603238]

EC 1.14.11.67

Accepted name: [histone H3]-trimethyl-L-lysin⁴ demethylase

Reaction: a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁴ + 3 2-oxoglutarate + 3 O₂ = a [histone H3]-L-lysine⁴ + 3 succinate + 3 formaldehyde + 3 CO₂ (overall reaction)
(1a) a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine⁴ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁴ + succinate + formaldehyde + CO₂
(1b) a [histone H3]-N⁶,N⁶-dimethyl-L-lysine⁴ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶-methyl-L-lysine⁴ + succinate + formaldehyde + CO₂
(1c) a [histone H3]-N⁶-methyl-L-lysine⁴ + 2-oxoglutarate + O₂ = a [histone H3]-L-lysine⁴ + succinate + formaldehyde + CO₂

Other name(s): KDM5A (gene name); KDM5B (gene name); KDM5C (gene name); KDM5D (gene name); JARID1A (gene name)

Systematic name: [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine-4,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 4 of histone H3 (H3K4). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri-, di-, and mono-methylated forms.

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

References:

1. Seward, D.J., Cubberley, G., Kim, S., Schonewald, M., Zhang, L., Tripet, B. and Bentley, D.L. Demethylation of trimethylated histone H3 Lys⁴ in vivo by JARID1 JmjC proteins. Nat. Struct. Mol. Biol. 14 (2007) 240-242. [PMID: 17310255]

2. Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y. and Kaelin, W.G., Jr. The retinoblastoma binding protein RBP2 is an H₃K4 demethylase. Cell 128 (2007) 889-900. [PMID: 17320163]

3. Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M. and Shi, Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128 (2007) 1077-1088. [PMID: 17320160]

4. Christensen, J., Agger, K., Cloos, P.A., Pasini, D., Rose, S., Sennels, L., Rappsilber, J., Hansen, K.H., Salcini, A.E. and Helin, K. RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell 128 (2007) 1063-1076. [PMID: 17320161]

EC 1.14.11.68

Accepted name: [histone H3]-trimethyl-L-lysine²⁷ demethylase

Reaction: a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine²⁷ + 2 2-oxoglutarate + 2 O₂ = a [histone H3]-N⁶-methyl-L-lysine²⁷ + 2 succinate + 2 formaldehyde + 2 CO₂ (overall reaction)
(1a) a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine²⁷ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶,N⁶-dimethyl-L-lysine²⁷ + succinate + formaldehyde + CO₂
(1b) a [histone H3]-N⁶,N⁶-dimethyl-L-lysine²⁷ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶-methyl-L-lysine²⁷ + succinate + formaldehyde + CO₂

Other name(s): KDM6A (gene name); KDM6C (gene name); UTX (gene name); UTY (gene name); JMJD3 (gene name)

Systematic name: [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine-27,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 27 of histone H3 (H3K27). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri- and di-methylated forms, but have no activity with the mono-methylated form.

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

References:

1. De Santa, F., Totaro, M.G., Prosperini, E., Notarbartolo, S., Testa, G. and Natoli, G. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell 130 (2007) 1083-1094. [PMID: 17825402]

2. Hong, S., Cho, Y.W., Yu, L.R., Yu, H., Veenstra, T.D. and Ge, K. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc. Natl Acad. Sci. USA 104 (2007) 18439-18444. [PMID: 18003914]

3. Lan, F., Bayliss, P.E., Rinn, J.L., Whetstine, J.R., Wang, J.K., Chen, S., Iwase, S., Alpatov, R., Issaeva, I., Canaani, E., Roberts, T.M., Chang, H.Y. and Shi, Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449 (2007) 689-694. [PMID: 17851529]

4. Lee, M.G., Villa, R., Trojer, P., Norman, J., Yan, K.P., Reinberg, D., Di Croce, L. and Shiekhattar, R. Demethylation of H₃K27 regulates polycomb recruitment and H2A ubiquitination. Science 318 (2007) 447-450. [PMID: 17761849]

5. Xiang, Y., Zhu, Z., Han, G., Lin, H., Xu, L. and Chen, C.D. JMJD3 is a histone H3K27 demethylase. Cell Res 17 (2007) 850-857. [PMID: 17923864]

EC 1.14.11.69

Accepted name: [histone H3]-trimethyl-L-lysine³⁶ demethylase

Reaction: a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine³⁶ + 2 2-oxoglutarate + 2 O₂ = a [histone H3]-N⁶-methyl-L-lysine³⁶ + 2 succinate + 2 formaldehyde + 2 CO₂ (overall reaction)
(1a) a [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine³⁶ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶,N⁶-dimethyl-L-lysine³⁶ + succinate + formaldehyde + CO₂
(1b) a [histone H3]-N⁶,N⁶-dimethyl-L-lysine³⁶ + 2-oxoglutarate + O₂ = a [histone H3]-N⁶-methyl-L-lysine³⁶ + succinate + formaldehyde + CO₂

Other name(s): KDM4A (gene name); KDM4B (gene name); RPH1 (gene name); JHDM3A (gene name); JHDM3B (gene name); JMJD2A (gene name); JMJD2B (gene name)

Systematic name: [histone H3]-N⁶,N⁶,N⁶-trimethyl-L-lysine-36,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys³⁶ residues in the tail of the histone protein H3 (H3K36). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. Since trimethylation of H3K36 enhances transcription, this enzyme acts as a transcription repressor. The enzymes that possess this activity often also catalyse the activity of EC 1.14.11.66, [histone H3]-trimethyl-L-lysine⁹ demethylase. cf. EC 1.14.11.27, [histone H3]-dimethyl-L-lysine³⁶ demethylase.

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

References:

1. Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G., Colaiacovo, M. and Shi, Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125 (2006) 467-481. [PMID: 16603238]

2. Klose, R.J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442 (2006) 312-316. [PMID: 16732292]

3. Kim, T. and Buratowski, S. Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys³⁶ in transcribed regions to promote elongation. J. Biol. Chem 282 (2007) 20827-20835. [PMID: 17525156]

4. Couture, J.F., Collazo, E., Ortiz-Tello, P.A., Brunzelle, J.S. and Trievel, R.C. Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase. Nat. Struct. Mol. Biol. 14 (2007) 689-695. [PMID: 17589523]

5. Lin, C.H., Li, B., Swanson, S., Zhang, Y., Florens, L., Washburn, M.P., Abmayr, S.M. and Workman, J.L. Heterochromatin protein 1a stimulates histone H3 lysine 36 demethylation by the Drosophila KDM4A demethylase. Mol. Cell 32 (2008) 696-706. [PMID: 19061644]

6. Colmenares, S.U., Swenson, J.M., Langley, S.A., Kennedy, C., Costes, S.V. and Karpen, G.H. Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity. Dev Cell 42 (2017) 156-169.e5. [PMID: 28743002]

EC 1.14.11.70

Accepted name: 7-deoxycylindrospermopsin hydroxylase

Reaction: (1) 7-deoxycylindrospermopsin + 2-oxoglutarate + O₂ = cylindrospermopsin + succinate + CO₂
(2) 7-deoxycylindrospermopsin + 2-oxoglutarate + O₂ = 7-epi-cylindrospermopsin + succinate + CO₂

Glossary: cylindrospermopsin = (2aS,3R,4S,5aS,7R)-7-[(R)-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)(hydroxy)methyl]-3-methyl-2a,3,4,5,5a,6,7,8-octahydro-2H-1,8,8b-triazaacenaphthylen-4-yl hydrogen sulfate

Other name(s): cyrI (gene name)

Systematic name: 7-deoxycylindrospermopsin, 2-oxoglutarate:oxygen oxidoreductase (7-hydroxylating)

Comments: Requires iron((II). The enzyme, found in some cyanobacterial species, catalyses the last step in the biosynthesis of the toxins cylindrospermopsin and 7-epi-cylindrospermopsin. The ratio of the two products differs among different strains.

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

References:

1. Mazmouz, R., Chapuis-Hugon, F., Pichon V., Mejean, A., and Ploux, O. The last step of the biosynthesis of the cyanotoxins cylindrospermopsin and 7-epi-cylindrospermopsin is catalysed by CyrI, a 2-oxoglutarate-dependent iron oxygenase. Chem. Biochem. 12 (2011) 858-862.

2. Mazmouz, R., Essadik, I., Hamdane, D., Mejean, A. and Ploux, O. Characterization of CyrI, the hydroxylase involved in the last step of cylindrospermopsin biosynthesis: Binding studies, site-directed mutagenesis and stereoselectivity. Arch. Biochem. Biophys. 647 (2018) 1-9. [PMID: 29653078]

EC 1.14.11.71

Accepted name: methylphosphonate hydroxylase

Reaction: methylphosphonate + 2-oxoglutarate + O₂ = hydroxymethylphosphonate + succinate + CO₂

Other name(s): phnY* (gene name)

Systematic name: methylphosphonate,2-oxoglutarate:oxygen oxidoreductase (1-hydroxylating)

Comments: Requires iron((II). The enzyme, characterized from the marine bacterium Gimesia maris, participates in a methylphosphonate degradation pathway.

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

References:

1. Gama, S.R., Vogt, M., Kalina, T., Hupp, K., Hammerschmidt, F., Pallitsch, K. and Zechel, D.L. An oxidative pathway for microbial utilization of methylphosphonic acid as a phosphate source. ACS Chem. Biol. 14 (2019) 735-741. [PMID: 30810303]

EC 1.14.11.72

Accepted name: [2-(trimethylamino)ethyl]phosphonate dioxygenase

Reaction: [2-(trimethylamino)ethyl]phosphonate + 2-oxoglutarate + O₂ = [(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate + succinate + CO₂

Other name(s): tmpA (gene name)

Systematic name: [2-(trimethylamino)ethyl]phosphonate,2-oxoglutarate:oxygen oxidoreductase (1R-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme, found in bacteria, participates in a degradation pathway for [2-(trimethylamino)ethyl]phosphonate.

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

References:

1. Rajakovich, L.J., Pandelia, M.E., Mitchell, A.J., Chang, W.C., Zhang, B., Boal, A.K., Krebs, C. and Bollinger, J.M., Jr. A new microbial pathway for organophosphonate degradation catalyzed by two previously misannotated non-heme-iron oxygenases. Biochemistry 58 (2019) 1627-1647. [PMID: 30789718]

EC 1.14.11.73

Accepted name: [protein]-arginine 3-hydroxylase

Reaction: [protein]-L-arginine + 2-oxoglutarate + O₂ = [protein]-(3R)-3-hydroxy-L-arginine + succinate + CO₂

Other name(s): JMJD5 (gene name)

Systematic name: [protein]-L-arginine,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)

Comments: The enzyme, characterized from humans, catalyses the stereoselective formation of the (2S,3R)-hydroxy-L-arginine stereoisomer. So far the enzyme has been shown to act on two substrates - the 40S ribosomal protein S6 (RPS6), which is hydroxylated at R137, and, at a lower activity, RCCD1, a protein involved in chromatin stability, which is hydroxylated at R141. Even though the same stereoisomer is produced by the bacterial EC 1.14.11.47, [50S ribosomal protein L16]-arginine 3-hydroxylase, the two enzymes do not exhibit any cross-reactivity on their respective ribosomal protein substrates.

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

References:

1. Wilkins, S.E., Islam, M.S., Gannon, J.M., Markolovic, S., Hopkinson, R.J., Ge, W., Schofield, C.J. and Chowdhury, R. JMJD5 is a human arginyl C-3 hydroxylase. Nat. Commun. 9 (2018) 1180. [PMID: 29563586]

EC 1.14.11.74

Accepted name: L-isoleucine 3¹-dioxygenase

Reaction: L-isoleucine + 2-oxoglutarate + O₂ = 3¹-hydroxy-L-isoleucine + succinate + CO₂

Other name(s): hilA (gene name); L-isoleucine 4'-dioxygenase (incorrect)

Systematic name: L-isoleucine, 2-oxoglutarate:oxygen oxidoreductase (3¹-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme has been characterized from the bacterium Pantoea ananatis.

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

References:

1. Smirnov, S.V., Sokolov, P.M., Kotlyarova, V.A., Samsonova, N.N., Kodera, T., Sugiyama, M., Torii, T., Hibi, M., Shimizu, S., Yokozeki, K. and Ogawa, J. A novel L-isoleucine-4'-dioxygenase and L-isoleucine dihydroxylation cascade in Pantoea ananatis. MicrobiologyOpen 2 (2013) 471-481. [PMID: 23554367]

EC 1.14.11.75

Accepted name: 3¹-hydroxy-L-isoleucine 4-dioxygenase

Reaction: 3¹-hydroxy-L-isoleucine + 2-oxoglutarate + O₂ = (4S)-3¹,4-dihydroxy-L-isoleucine + succinate + CO₂

Other name(s): hilB (gene name); 4'-hydroxy-L-isoleucine 4-dioxygenase (incorrect)

Systematic name: 3¹-hydroxy-L-isoleucine, 2-oxoglutarate:oxygen oxidoreductase (4S-hydroxylating)

Comments: Requires Fe²⁺ and ascorbate. The enzyme has been characterized from the bacterium Pantoea ananatis.

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

References:

1. Smirnov, S.V., Sokolov, P.M., Kotlyarova, V.A., Samsonova, N.N., Kodera, T., Sugiyama, M., Torii, T., Hibi, M., Shimizu, S., Yokozeki, K. and Ogawa, J. A novel L-isoleucine-4'-dioxygenase and L-isoleucine dihydroxylation cascade in Pantoea ananatis. MicrobiologyOpen 2 (2013) 471-481. [PMID: 23554367]

EC 1.14.11.76

Accepted name: L-glutamate 3(R)-hydroxylase

Reaction: L-glutamate + 2-oxoglutarate + O₂ = (3R)-3-hydroxy-L-glutamate + succinate + CO₂

Glossary: ibotenate = (S)-2-amino-2-(3-hydroxyisoxazol-5-yl)acetate
muscimol = 5-(aminomethyl)-1,2-oxazol-3-ol

Other name(s): iboH (gene name)

Systematic name: L-glutamate,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)

Comments: Requires Fe²⁺ and L-ascorbate. The enzyme, characterized from the basidiomycete mushroom Amanita muscaria, participates in the biosynthesis of the psychoactive compounds ibotenate and muscimol.

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

References:

1. Muller, M. and Obermaier, S. Ibotenic acid biosynthesis in the fly agaric is initiated by glutamate hydroxylation. Angew. Chem. Int. Ed. Engl. 59 (2020) 12432-12435. [PMID: 32233056]

EC 1.14.11.77

Accepted name: alkyl sulfatase

Reaction: a primary alkyl sulfate ester + 2-oxoglutarate + O₂ = an aldehyde + succinate + CO₂ + sulfate

Other name(s): atsK (gene name); α-ketoglutarate-dependent sulfate ester dioxygenase; 2-oxoglutarate-dependent sulfate ester dioxygenase; type II alkyl sulfatase

Systematic name: primary alkyl sulfate ester, 2-oxoglutarate:oxygen oxidoreductase (sulfate-hydrolyzing)

Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. The type II sulfatases oxidize the C-H bond of the carbon next to the sulfate ester, using 2-oxoglutarate and oxygen as substrates. The resulting hemiacetal sulfate ester collapses, liberating inorganic sulfate and an alkyl aldehyde along with carbon dioxide and succinate. The enzymes often desulfate a broad spectrum of linear and branched-chain sulfate esters. The enzyme from Pseudomonas putida acts on a range of medium-chain alkyl sulfate esters, with chain lengths ranging from C₄ to C₁₂. cf. sulfatase EC 3.1.6.1, arylsulfatase (type I), EC 3.1.6.21, linear primary-alkylsulfatase, and EC 3.1.6.22, branched primary-alkylsulfatase.

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

References:

1. Kahnert, A. and Kertesz, M.A. Characterization of a sulfur-regulated oxygenative alkylsulfatase from Pseudomonas putida S-313. J. Biol. Chem. 275 (2000) 31661-31667. [PMID: 10913158]

2. Muller, I., Kahnert, A., Pape, T., Sheldrick, G.M., Meyer-Klaucke, W., Dierks, T., Kertesz, M. and Uson, I. Crystal structure of the alkylsulfatase AtsK: insights into the catalytic mechanism of the Fe(II) α-ketoglutarate-dependent dioxygenase superfamily. Biochemistry 43 (2004) 3075-3088. [PMID: 15023059]

3. Sogi, K.M., Gartner, Z.J., Breidenbach, M.A., Appel, M.J., Schelle, M.W. and Bertozzi, C.R. Mycobacterium tuberculosis Rv3406 is a type II alkyl sulfatase capable of sulfate scavenging. PLoS One 8 (2013) e65080. [PMID: 23762287]

EC 1.14.11.78

Accepted name: (R)-3-[(carboxymethyl)amino]fatty acid dioxygenase/decarboxylase

Reaction: a (3R)-3-[(carboxylmethyl)amino]fatty acid + 2 2-oxoglutarate + 2 O₂ = a (3R)-3-isocyanyl-fatty acid + 2 succinate + 3 CO₂ + 2 H₂O (overall reaction)
(1a) a (3R)-3-[(carboxylmethyl)amino]fatty acid + 2-oxoglutarate + O₂ = a (3R)-3-{[carboxy(hydroxy)methyl]amino}fatty acid + succinate + CO₂
(1b) a (3R)-3-{[carboxy(hydroxy)methyl]amino}fatty acid + 2-oxoglutarate + O₂ = a (3R)-3-isocyanyl-fatty acid + succinate + 2 CO₂ + 2 H₂O

Other name(s): scoE (gene name); mmaE (gene name); Rv0097 (locus name)

Systematic name: (3R)-3-[(carboxylmethyl)amino]fatty acid,2-oxoglutarate:oxygen oxidoreductase (isonitrile-forming)

Comments: Requires Fe(II). The enzyme, found in actinobacterial species, participates in the biosynthesis of isonitrile-containing lipopeptides. The reaction comprises two catalytic cycles, each consuming an oxygen molecule and a 2-oxoglutarate molecule. In the first cycle the substrate is hydroxylated, while in the second cycle the enzyme catalyses a decarboxylation/oxidation reaction that produces an isonitrile group.

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

References:

1. Harris, N.C., Sato, M., Herman, N.A., Twigg, F., Cai, W., Liu, J., Zhu, X., Downey, J., Khalaf, R., Martin, J., Koshino, H. and Zhang, W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc. Natl. Acad. Sci. USA 114 (2017) 7025-7030. [PMID: 28634299]

2. Harris, N.C., Born, D.A., Cai, W., Huang, Y., Martin, J., Khalaf, R., Drennan, C.L. and Zhang, W. Isonitrile formation by a non-heme iron(II)-dependent oxidase/decarboxylase. Angew. Chem. Int. Ed. Engl. 57 (2018) 9707-9710. [PMID: 29906336]

3. Jonnalagadda, R., Del Rio Flores, A., Cai, W., Mehmood, R., Narayanamoorthy, M., Ren, C., Zaragoza, J.PT., Kulik, H.J., Zhang, W. and Drennan, C.L. Biochemical and crystallographic investigations into isonitrile formation by a nonheme iron-dependent oxidase/decarboxylase. J. Biol. Chem. 296 (2021) 100231. [PMID: 33361191]

EC 1.14.11.79

Accepted name: protein-L-histidine (3S)-3-hydroxylase

Reaction: a [protein]-L-histidine + 2-oxoglutarate + O₂ = a [protein]-(3S)-3-hydroxy-L-histidine + succinate + CO₂

Other name(s): RIOX1 (gene name); RIOX2 (gene name); protein histidyl hydroxylase

Systematic name: protein-L-histidine,2-oxoglutarate:oxygen oxidoreductase (3S-hydroxylating)

Comments: The human enzymes encoded by the RIOX1 and RIOX2 genes catalyse the hydroxylation of L-histidine residues in the 60S ribosomal proteins Rpl8 and L27a, respectively. Both proteins contain JmjC and winged helix domains, and both also catalyse histone L-lysine demethylation activities.

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

References:

1. Ge, W., Wolf, A., Feng, T., Ho, C.H., Sekirnik, R., Zayer, A., Granatino, N., Cockman, M.E., Loenarz, C., Loik, N.D., Hardy, A.P., Claridge, T.DW., Hamed, R.B., Chowdhury, R., Gong, L., Robinson, C.V., Trudgian, D.C., Jiang, M., Mackeen, M.M., Mccullagh, J.S., Gordiyenko, Y., Thalhammer, A., Yamamoto, A., Yang, M., Liu-Yi, P., Zhang, Z., Schmidt-Zachmann, M., Kessler, B.M., Ratcliffe, P.J., Preston, G.M., Coleman, M.L. and Schofield, C.J. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans. Nat. Chem. Biol. 8 (2012) 960-962. [PMID: 23103944]

2. Bundred, J.R., Hendrix, E. and Coleman, M.L. The emerging roles of ribosomal histidyl hydroxylases in cell biology, physiology and disease. Cell. Mol. Life Sci. 75 (2018) 4093-4105. [PMID: 30151692]

EC 1.14.11.80

Accepted name: methylcytosine dioxygenase

Reaction: (1) 5-methylcytosine in DNA + 2-oxoglutarate + O₂ = 5-hydroxymethylcytosine in DNA + succinate + CO₂
(2) 5-hydroxymethylcytosine in DNA + 2-oxoglutarate + O₂ = 5-formylcytosine in DNA + succinate + CO₂ + H₂O
(3) 5-formylcytosine in DNA + 2-oxoglutarate + O₂ = 5-carboxycytosine in DNA + succinate + CO₂

Other name(s): TET1 (gene name); TET2 (gene name); TET3 (gene name)

Systematic name: 5-methylcytosine in DNA,2-oxoglutarate:oxygen oxidoreductase

Comments: The TET proteins mediate iterative oxidation of 5-methylcytosine in DNA (5mc) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are recognized by EC 3.2.2.29, thymine-DNA glycosylase (TDG), which excises them, leaving an apyrimidinic site. Coupled with the base excision repair (BER) pathway, these activities result in a cytosine demethylation pathway.

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

References:

1. Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C. and Zhang, Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466 (2010) 1129-1133. [PMID: 20639862]

2. Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C. and Zhang, Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333 (2011) 1300-1303. [PMID: 21778364]

3. He, Y.F., Li, B.Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.X., Zhang, K., He, C. and Xu, G.L. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333 (2011) 1303-1307. [PMID: 21817016]

4. Maiti, A. and Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J. Biol. Chem. 286 (2011) 35334-35338. [PMID: 21862836]

5. Zhang, L., Lu, X., Lu, J., Liang, H., Dai, Q., Xu, G.L., Luo, C., Jiang, H. and He, C. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol. 8 (2012) 328-330. [PMID: 22327402]

EC 1.14.11.81

Accepted name: (–)-cyclopenine synthase

Reaction: (1) cyclopeptine + 2-oxoglutarate + O₂ = dehydrocyclopeptine + succinate + CO₂ + H₂O
(2) dehydrocyclopeptine + 2-oxoglutarate + O₂ = (–)-cyclopenine + succinate + CO₂

For reaction pathway click here.

Glossary: cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
(–)-cyclopenine = (3S,3'R)-4-methyl-3'-phenyl-1H-spiro[1,4-benzodiazepine-3,2'-oxirane]-2,5-dione

Other name(s): asqJ (gene name)

Systematic name: cyclopeptine,2-oxoglutarate:oxygen oxidoreductase ((–)-cyclopenine-forming)

Comments: This fungal enzyme is involved in the biosynthesis of quinolone compounds. it catalyses two oxidation reactions: the first reaction results in a desaturation; the second reaction is a monooxygenation of the double bond, forming an epoxide. The enzyme is also active with 4'-methoxycyclopeptine.

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

References:

1. Nover, L. and Luckner, M. Mixed functional oxygenations during the biosynthesis of cyclopenin and cyclopenol, benzodiazepine alkaloids of Penicillium cyclopium westling. Incorporation of molecular oxygen and NIH-shift. FEBS Lett. 3 (1969) 292-296. [PMID: 11947032]

2. Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880-12884. [PMID: 25251934]

3. Brauer, A., Beck, P., Hintermann, L. and Groll, M. Structure of the dioxygenase AsqJ: Mechanistic insights into a one-pot multistep quinolone antibiotic biosynthesis. Angew. Chem. Int. Ed. Engl. 55 (2016) 422-426. [PMID: 26553478]

4. Chang, W.C., Li, J., Lee, J.L., Cronican, A.A. and Guo, Y. Mechanistic investigation of a non-heme iron enzyme catalyzed epoxidation in (–)-4'-methoxycyclopenin biosynthesis. J. Am. Chem. Soc. 138 (2016) 10390-10393. [PMID: 27442345]

5. Song, X., Lu, J. and Lai, W. Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations. Phys Chem Chem Phys 19 (2017) 20188-20197. [PMID: 28726913]

6. Liao, H.J., Li, J., Huang, J.L., Davidson, M., Kurnikov, I., Lin, T.S., Lee, J.L., Kurnikova, M., Guo, Y., Chan, N.L. and Chang, W.C. Insights into the desaturation of cyclopeptin and its C₃ epimer catalyzed by a non-heme Iron enzyme: structural characterization and mechanism elucidation. Angew. Chem. Int. Ed. Engl. 57 (2018) 1831-1835. [PMID: 29314482]

7. Mader, S.L., Brauer, A., Groll, M. and Kaila, V.RI. Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ. Nat. Commun. 9 (2018) 1168. [PMID: 29563492]

8. Wojdyla, Z. and Borowski, T. On how the binding cavity of AsqJ dioxygenase controls the desaturation reaction regioselectivity: a QM/MM study. J. Biol. Inorg. Chem. 23 (2018) 795-808. [PMID: 29876666]

9. Li, J., Liao, H.J., Tang, Y., Huang, J.L., Cha, L., Lin, T.S., Lee, J.L., Kurnikov, I.V., Kurnikova, M.G., Chang, W.C., Chan, N.L. and Guo, Y. Epoxidation catalyzed by the nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase, AsqJ: mechanistic elucidation of oxygen atom transfer by a ferryl intermediate. J. Am. Chem. Soc. 142 (2020) 6268-6284. [PMID: 32131594]

10. Tang, H., Tang, Y., Kurnikov, I.V., Liao, H.J., Chan, N.L., Kurnikova, M.G., Guo, Y. and Chang, W.C. Harnessing the substrate promiscuity of dioxygenase AsqJ and developing efficient chemoenzymatic synthesis for quinolones. ACS Catal. 11 (2021) 7186-7192. [PMID: 35721870]

EC 1.14.11.82

Accepted name: 5-dehydro-6-demethoxyfumagillol dioxygenase

Reaction: 5-dehydro-6-demethoxyfumagillol + 2-oxoglutarate + O₂ = 5-dehydro-6-demethoxy-6-hydroxyfumagillol + succinate + CO₂

For diagram of reaction click here

Glossary: fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol

Other name(s): fmaF (gene name); Fma-C6H

Systematic name: 5-dehydro-6-demethoxyfumagillol,2-oxoglutarate:oxygen oxidoreductase (6-hydroxylating)

Comments: Requires iron(II). The enzyme, characterized from the mold Aspergillus fumigatus, participates in the biosynthesis of the meroterpenoid fumagillin.

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

References:

1. Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426-4436. [PMID: 24568283]

Contents

Accepted name: anthranilate 1,2-dioxygenase (deaminating, decarboxylating)

Reaction: anthranilate + NAD(P)H + 2 H⁺ + O₂ = catechol + CO₂ + NAD(P)⁺ + NH₃

For diagram of reaction click here.

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

Systematic name: anthranilate,NAD(P)H:oxygen oxidoreductase (1,2-hydroxylating, deaminating, decarboxylating)

Comments: Requires Fe²⁺.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 9059-17-0

References:

1. Kobayashi, S. and Hayaishi, O. Anthranilic acid conversion to catechol (Pseudomonas). Methods Enzymol. 17A (1970) 505-510.

2. Taniguchi, H., Hatanaka, M., Kuno, S., Hayaishi, O., Nakajima, M. and Kurihara, N. Enzymatic formation of catechol from anthranilic acid. J. Biol. Chem. 239 (1964) 2204-2211.

[EC 1.14.12.2 Transferred entry: now EC 1.14.13.35 anthranilate 3-monooxygenase (deaminating) (EC 1.14.12.2 created 1972, deleted 1990)]

EC 1.14.12.3

Accepted name: benzene 1,2-dioxygenase

Reaction: benzene + NADH + H⁺ + O₂ = cis-cyclohexa-3,5-diene-1,2-diol + NAD⁺

For diagram click here.

Other name(s): benzene hydroxylase; benzene dioxygenase

Systematic name: benzene,NADH:oxygen oxidoreductase (1,2-hydroxylating)

Comments: A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), an iron-sulfur oxygenase and ferredoxin. Requires Fe²⁺.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9075-66-5

References:

1. Gibson, D.T., Koch, J.R. and Kallio, R.E. Oxidative degradation of aromatic hydrocarbons by microorganisms. I. Enzymatic formation of catechol from benzene. Biochemistry 7 (1968) 2653-2662. [PMID: 4298226]

[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 1.14.12.6 Transferred entry: now EC 1.14.13.66 2-hydroxycyclohexanone 2-monooxygenase (EC 1.14.12.6 created 1978, deleted 1999)]

EC 1.14.12.7

Accepted name: phthalate 4,5-dioxygenase

Reaction: phthalate + NADH + H⁺ + O₂ = cis-4,5-dihydroxycyclohexa-1(6),2-diene-1,2-dicarboxylate + NAD⁺

For diagram click here.

Other name(s): PDO ; phthalate dioxygenase

Systematic name: phthalate,NADH:oxygen oxidoreductase (4,5-hydroxylating)

Comments: A system, containing a reductase which is an iron-sulfur flavoprotein (FMN), an iron-sulfur oxygenase, and no independent ferredoxin. Requires Fe²⁺.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 63626-44-8

References:

1. Batie, C.J., Lattaie, E. and Ballou, D.P. Purification and characterization of phthalate oxygenase and phthalate oxygenase reductase from Pseudomonas cepacia. J. Biol. Chem. 262 (1987) 1510-1518. [PMID: 3805038]

EC 1.14.12.8

Accepted name: 4-sulfobenzoate 3,4-dioxygenase

Reaction: 4-sulfobenzoate + NADH + H⁺ + O₂ = 3,4-dihydroxybenzoate + sulfite + NAD⁺

For diagram click here.

Other name(s): 4-sulfobenzoate dioxygenase; 4-sulfobenzoate 3,4-dioxygenase system

Systematic name: 4-sulfobenzoate,NADH:oxygen oxidoreductase (3,4-hydroxylating, sulfite-forming)

Comments: A system, containing a reductase which is an iron-sulfur flavoprotein (FMN), an iron-sulfur oxygenase, and no independent ferredoxin. Requires Fe²⁺.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 122933-81-7

References:

1. Locher, H.H., Leisinger, T. and Cook, A.M. 4-Sulphobenzoate 3,4-dioxygenase. Purification and properties of a desulphonative two-component enzyme system from Comamonas testosteroni T-2. Biochem. J. 274 (1991) 833-842. [PMID: 2012609]

EC 1.14.12.9

Accepted name: 4-chlorophenylacetate 3,4-dioxygenase

Reaction: 4-chlorophenylacetate + NADH + H⁺ + O₂ = 3,4-dihydroxyphenylacetate + chloride + NAD⁺

For diagram click here.

Systematic name: 4-chlorophenylacetate,NADH:oxygen oxidoreductase (3,4-hydroxylating, dechlorinating)

Comments: A system, containing a reductase and an iron-sulfur oxygenase, and no independent ferredoxin. Requires Fe²⁺. Also acts on 4-bromophenyl acetate.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 105006-00-6

References:

1. Markus, A., Krekel, D. and Lingens, F. Purification and some properties of component A of the 4-chlorophenylacetate 3,4-dioxygenase from Pseudomonas species strain CBS. J. Biol. Chem. 261 (1986) 12883-12888. [PMID: 3745216]

EC 1.14.12.10

Accepted name: benzoate 1,2-dioxygenase

Reaction: benzoate + NADH + H⁺ + O₂ = (1R,6S)-1,6-dihydroxycyclohexa-2,4-diene-1-carboxylate + NAD⁺

For diagram click here (another example).

Other name(s): benzoate hydroxylase; benzoate hydroxylase; benzoic hydroxylase; benzoate dioxygenase; benzoate,NADH:oxygen oxidoreductase (1,2-hydroxylating, decarboxylating) [incorrect]

Systematic name: benzoate,NADH:oxygen oxidoreductase (1,2-hydroxylating)

Comments: A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), and an iron-sulfur oxygenase. Requires Fe²⁺.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9059-18-1

References:

1. Yamaguchi, M. and Fujisawa, H. Characterization of NADH-cytochrome c reductase, a component of benzoate 1,2-dioxygenase system from Pseudomonas arvilla C-1. J. Biol. Chem. 253 (1978) 8848-8853. [PMID: 214433]

2. Yamaguchi, M. and Fujisawa, H. Purification and characterization of an oxygenase component in benzoate 1,2-dioxygenase system from Pseudomonas arvilla C-1. J. Biol. Chem. 255 (1980) 5058-5063. [PMID: 7372624]

3. Yamaguchi, M. and Fujisawa, H. Subunit structure of oxygenase component in benzoate-1,2-dioxygenase system from Pseudomonas arvilla C-1. J. Biol. Chem. 257 (1982) 12497-12502. [PMID: 7130163]

EC 1.14.12.11

Accepted name: toluene dioxygenase

Reaction: toluene + NADH + H⁺ + O₂ = (1S,2R)-3-methylcyclohexa-3,5-diene-1,2-diol + NAD⁺

For diagram click here.

Other name(s): toluene 2,3-dioxygenase

Systematic name: toluene,NADH:oxygen oxidoreductase (1,2-hydroxylating)

Comments: A system, containing a reductase which is an iron-sulfur flavoprotein (FAD), an iron-sulfur oxygenase, and a ferredoxin. Some other aromatic compounds, including ethylbenzene, 4-xylene and some halogenated toluenes, are converted into the corresponding cis-dihydrodiols.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 120038-36-0

References:

1. Renganathan, V. Possible involvement of toluene-2,3-dioxygenase in defluorination of 3-fluoro-substituted benzenes by toluene-degrading Pseudomonas sp. strain T-12. Appl. Exp. Microbiol. 55 (1989) 330-334.

2. Subramanian, V., Liu, T.-N., Yeh, W.K. and Gibson, D.T. Toluene dioxygenase: purification of an iron-sulfur protein by affinity chromatography. Biochem. Biophys. Res. Commun. 91 (1979) 1131-1139. [PMID: 526270]

EC 1.14.12.12

Accepted name: naphthalene 1,2-dioxygenase

Reaction: naphthalene + NADH + H⁺ + O₂ = (1R,2S)-1,2-dihydronaphthalene-1,2-diol + NAD⁺

For diagram of reaction click here and related reactions click here.

Other name(s): naphthalene dioxygenase; naphthalene oxygenase

Systematic name: naphthalene,NADH:oxygen oxidoreductase (1,2-hydroxylating)

Comments: This enzyme is a member of the ring-hydroxylating dioxygenase (RHD) family of bacterial enzymes that play a critical role in the degradation of aromatic compounds, such as polycyclic aromatic hydrocarbons [5]. This enzyme comprises a multicomponent system, containing a reductase that is an iron-sulfur flavoprotein (FAD; EC 1.18.1.3, ferredoxin—NAD⁺ reductase), an iron-sulfur oxygenase, and ferredoxin. Requires Fe²⁺.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9074-04-8

References:

1. Ensley, B.D. and Gibson, D.T. Naphthalene dioxygenase: purification and properties of a terminal oxygenase component. J. Bacteriol. 155 (1983) 505-511. [PMID: 6874638]

2. Jeffrey, A.M., Yeh, H.J.C., Jerina, D.M., Patel, T.R., Davey, J.F. and Gibson, D.T. Initial reactions in the oxidation of naphthalene by Pseudomonas putida. Biochemistry 14 (1975) 575-584. [PMID: 234247]

3. Kauppi, B., Lee, K., Carredano, E., Parales, R.E., Gibson, D.T., Eklund, H. and Ramaswamy, S. Structure of an aromatic-ring-hydroxylating dioxygenase - naphthalene 1,2-dioxygenase. Structure 6 (1998) 571-586. [PMID: 9634695]

4. Parales, R.E., Lee, K., Resnick, S.M., Jiang, H., Lessner, D.J. and Gibson, D.T. Substrate specificity of naphthalene dioxygenase: effect of specific amino acids at the active site of the enzyme. J. Bacteriol. 182 (2000) 1641-1649. [PMID: 10692370]

5. Jouanneau, Y., Meyer, C., Jakoncic, J., Stojanoff, V. and Gaillard, J. Characterization of a naphthalene dioxygenase endowed with an exceptionally broad substrate specificity toward polycyclic aromatic hydrocarbons. Biochemistry 45 (2006) 12380-12391. [PMID: 17014090]

EC 1.14.12.13

Accepted name: 2-halobenzoate 1,2-dioxygenase

Reaction: a 2-halobenzoate + NADH + H⁺ + O₂ = catechol + a halide anion + NAD⁺ + CO₂

For diagram of reaction click here and mechanism click here.

Other name(s): 2-chlorobenzoate 1,2-dioxygenase

Systematic name: 2-halobenzoate,NADH:oxygen oxidoreductase (1,2-hydroxylating, dehalogenating, decarboxylating)

Comments: A multicomponent enzyme system composed of a dioxygenase component and an electron transfer component. The latter contains FAD. The enzyme, characterized from the bacterium Burkholderia cepacia 2CBS, has a broad substrate specificity. Substrates include 2-fluorobenzoate, 2-chlorobenzoate, 2-bromobenzoate, and 2-iodobenzoate, which are processed in this order of preference.

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 125268-83-9

References:

1. Fetzner, S., Mueller, R. and Lingens, F. Degradation of 2-chlorobenzoate by Pseudomonas cepacia 2CBS. Biol. Chem. Hoppe-Seyler 370 (1989) 1173-1182. [PMID: 2610934]

2. Fetzner, S., Muller, R. and Lingens, F. Purification and some properties of 2-halobenzoate 1,2-dioxygenase, a two-component enzyme system from Pseudomonas cepacia 2CBS. J. Bacteriol. 174 (1992) 279-290. [PMID: 1370284]

3. Haak, B., Fetzner, S. and Lingens, F. Cloning, nucleotide sequence, and expression of the plasmid-encoded genes for the two-component 2-halobenzoate 1,2-dioxygenase from Pseudomonas cepacia 2CBS. J. Bacteriol. 177 (1995) 667-675. [PMID: 7530709]

EC 1.14.12.14

Accepted name: 2-aminobenzenesulfonate 2,3-dioxygenase

Reaction: 2-aminobenzenesulfonate + NADH + H⁺ + O₂ = 2,3-dihydroxybenzenesulfonate + NH₃ + NAD⁺

For diagram click here.

Other name(s): 2-aminosulfobenzene 2,3-dioxygenase

Systematic name: 2-aminobenzenesulfonate,NADH:oxygen oxidoreductase (2,3-hydroxylating, ammonia-forming)

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 156621-16-8

References:

1. Junker, F., Field, J.A., Bangerter, F., Ramsteiner, K., Kohler, H.-P., Joannou, C.L., Mason, J.R., Leisinger, T. and Cook, A.M. Dioxygenation and spontaneous deamination of 2-aminobenzene sulphonic acid in Alcaligenes sp. strain O-1 with subsequent meta ring cleavage and spontaneous desulphonation to 2-hydroxymuconic acid. Biochem. J. 300 (1994) 429-436. [PMID: 8002948]

2. Junker, F., Leisinger, T. and Cook, A.M. 3-Sulphocatechol dioxygenase and other dioxygenases (1.13.11.2 and 1.14.12.-) in the degradative pathways of 2-aminobenzenesulphonic, benzenesulphonic and 4-toluenesulphonic acids in Alcaligenes sp. strain O-1. J. Gen. Microbiol. 140 (1994) 1713-1722. [PMID: 8075807]

EC 1.14.12.15

Accepted name: terephthalate 1,2-dioxygenase

Reaction: terephthalate + NADH + H⁺ + O₂ = (1R,6S)-dihydroxycyclohexa-2,4-diene-1,4-dicarboxylate + NAD⁺

For diagram click here.

Other name(s): benzene-1,4-dicarboxylate 1,2-dioxygenase; 1,4-dicarboxybenzoate 1,2-dioxygenase

Systematic name: benzene-1,4-dicarboxylate,NADH:oxygen oxidoreductase (1,2-hydroxylating)

Comments: has been shown to contain a Rieske [2Fe-2S] cluster

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 162032-76-0

References:

1. Schläfli, H.R., Weiss, M.A., Leisinger, T. and Cook, A.M. Terephthalate 1,2-dioxygenase system from Comamonas testosteroni T-2; purification and some properties of the oxygenase component. J. Bacteriol. 176 (1994) 6644-6652. [PMID: 7961417]

EC 1.14.12.16

Accepted name: 2-hydroxyquinoline 5,6-dioxygenase

Reaction: quinolin-2-ol + NADH + H⁺ + O₂ = 2,5,6-trihydroxy-5,6-dihydroquinoline + NAD⁺

For diagram click here.

Other name(s): 2-oxo-1,2-dihydroquinoline 5,6-dioxygenase; quinolin-2-ol 5,6-dioxygenase; quinolin-2(1H)-one 5,6-dioxygenase

Systematic name: quinolin-2-ol,NADH:oxygen oxidoreductase (5,6-hydroxylating)

Comments: 3-Methylquinolin-2-ol, quinolin-8-ol and quinolin-2,8-diol are also substrates. Quinolin-2-ols exist largely as their quinolin-2(1H)-one tautomers

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, CAS registry number: 172399-50-7

References:

1. Schach, S.B., Tshisuaka, B., Fetzner, S. and Lingens, F. Quinoline 2-oxidoreductase and 2-oxo-1,2-dihydroquinoline 5,6-dioxygenase from Comamonas testosteroni 63. The first two enzymes in quinoline and 3-methylquinoline degradation. Eur. J. Biochem. 232 (1995) 536-544. [PMID: 7556204]

EC 1.14.12.17

Accepted name: nitric oxide dioxygenase

Reaction: 2 nitric oxide + 2 O₂ + NAD(P)H = 2 nitrate + NAD(P)⁺ + H⁺

Glossary: nitric oxide = NO

Systematic name: nitric oxide,NAD(P)H:oxygen oxidoreductase

Comments: A flavohemoglobin (FAD). It has been proposed that FAD functions as the electron carrier from NADPH to the ferric heme cofactor.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 214466-78-1

References:

1. Gardner, P.R., Costantino, G. and Salzman, A.L. Constitutive and adaptive detoxification of nitric oxide in Escherichia coli. Role of nitric-oxide dioxygenase in the protection of aconitase. J. Biol. Chem. 273 (1998) 26528-26533. [PMID: 9756889]

2. Gardner, P.R., Gardner, A.M., Martin, L.A. and Salzman, A.L. Nitric oxide dioxygenase: an enzymic function for flavohemoglobin. Proc. Natl. Acad. Sci. USA 95 (1998) 10378-10383. [PMID: 9724711]

EC 1.14.12.18

Accepted name: biphenyl 2,3-dioxygenase

Reaction: biphenyl + NADH + H⁺ + O₂ = (1S,2R)-3-phenylcyclohexa-3,5-diene-1,2-diol + NAD⁺

For reaction pathway click here.

Other name(s): biphenyl dioxygenase

Systematic name: biphenyl,NADH:oxygen oxidoreductase (2,3-hydroxylating)

Comments: Requires Fe²⁺. The enzyme from Burkholderia fungorum LB400 (previously Pseudomonas sp.) is part of a multicomponent system composed of an NADH:ferredoxin oxidoreductase (FAD cofactor), a [2Fe-2S] Rieske-type ferredoxin, and a terminal oxygenase that contains a [2Fe-2S] Rieske-type iron-sulfur cluster and a catalytic mononuclear nonheme iron centre. Chlorine-substituted biphenyls can also act as substrates. Similar to the three-component enzyme systems EC 1.14.12.3 (benzene 1,2-dioxygenase) and EC 1.14.12.11 (toluene dioxygenase).

Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 103289-55-0

References:

1. Haddock, J.D. and Gibson, D.T. Purification and characterization of the oxygenase component of biphenyl 2,3-dioxygenase from Pseudomonas sp. strain LB400. J. Bacteriol. 177 (1995) 5834-5839. [PMID: 7592331]

2. Haddock, J.D., Pelletier, D.A. and Gibson, D.T. Purification and properties of ferredoxinBPH, a component of biphenyl 2,3-dioxygenase of Pseudomonas sp. strain LB400. J. Indust. Microbiol. Biotechnol. 19 (1997) 355-359. [PMID: 9451832]

3. Broadus, R.M. and Haddock, J.D. Purification and characterization of the NADH:ferredoxinBPH oxidoreductase component of biphenyl 2,3-dioxygenase from Pseudomonas sp. strain LB400. Arch. Microbiol. 170 (1998) 106-112. [PMID: 9683647]

EC 1.14.12.19

Accepted name: 3-phenylpropanoate dioxygenase

Reaction: (1) 3-phenylpropanoate + NADH + H⁺ + O₂ = 3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate + NAD⁺
(2) (2E)-3-phenylprop-2-enoate + NADH + H⁺ + O₂ = (2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate + NAD⁺

For diagram of reaction, click here or click here

Glossary: (2E)-3-phenylprop-2-enoate = trans-cinnamate
(2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate = trans-2,3-dihydroxycinnamate

Other name(s): HcaA1A2CD; Hca dioxygenase; 3-phenylpropionate dioxygenase

Systematic name: 3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating)

Comments: This enzyme catalyses a step in the pathway of phenylpropanoid compounds degradation. It catalyses the insertion of both atoms of molecular oxygen into positions 2 and 3 of the phenyl ring of 3-phenylpropanoate or (2E)-3-phenylprop-2-enoate.

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

References:

1. Díaz, E., Ferrández, A. and García, J.L. Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12. J. Bacteriol. 180 (1998) 2915-2923. [PMID: 9603882]

2. Burlingame, R. and Chapman, P.J. Catabolism of phenylpropionic acid and its 3-hydroxy derivative by Escherichia coli. J. Bacteriol. 155 (1983) 113-121. [PMID: 6345502]

[EC 1.14.12.20 Transferred entry: pheophorbide a oxygenase, now classified as EC 1.14.15.17, pheophorbide a oxygenase. (EC 1.14.12.20 created 2007, deleted 2016)]

[EC 1.14.12.21 Transferred entry: benzoyl-CoA 2,3-dioxygenase. Now EC 1.14.13.208, benzoyl-CoA 2,3-epoxidase (EC 1.14.12.21 created 2010, deleted 2015)]

EC 1.14.12.22

Accepted name: carbazole 1,9a-dioxygenase

Reaction: 9H-carbazole + NAD(P)H + H⁺ + O₂ = 2'-aminobiphenyl-2,3-diol + NAD(P)⁺

Other name(s): CARDO

Systematic name: 9H-carbazole,NAD(P)H:oxygen oxidoreductase (2,3-hydroxylating)

Comments: This enzyme catalyses the first reaction in the pathway of carbazole degradation. The enzyme attacks at the 1 and 9a positions of carbazle, resulting in the formation of a highly unstable hemiaminal intermediate that undergoes a spontaneous cleavage and rearomatization, resulting in 2'-aminobiphenyl-2,3-diol. In most bacteria the enzyme is a complex composed of a terminal oxygenase, a ferredoxin, and a ferredoxin reductase. The terminal oxygenase component contains a nonheme iron centre and a Rieske [2Fe-2S] iron-sulfur cluster.

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

References:

1. Nam, J.W., Nojiri, H., Noguchi, H., Uchimura, H., Yoshida, T., Habe, H., Yamane, H. and Omori, T. Purification and characterization of carbazole 1,9a-dioxygenase, a three-component dioxygenase system of Pseudomonas resinovorans strain CA10. Appl. Environ. Microbiol. 68 (2002) 5882-5890. [PMID: 12450807]

2. Gai, Z., Wang, X., Liu, X., Tai, C., Tang, H., He, X., Wu, G., Deng, Z. and Xu, P. The genes coding for the conversion of carbazole to catechol are flanked by IS6100 elements in Sphingomonas sp. strain XLDN2-5. PLoS One 5 (2010) e10018. [PMID: 20368802]

EC 1.14.12.23

Accepted name: nitroarene dioxygenase

Reaction: nitrobenzene + NADH + O₂ = catechol + nitrite + NAD⁺

For diagram of reaction click here.

Other name(s): cnbA (gene name)

Systematic name: nitrobenzene,NADH:oxygen oxidoreductase (1,2-hydroxylating, nitrite-releasing)

Comments: This enzyme is a member of the naphthalene family of bacterial Rieske non-heme iron dioxygenases. It comprises a multicomponent system, containing a Rieske [2Fe-2S] ferredoxin, an NADH-dependent flavoprotein reductase (EC 1.18.1.3, ferredoxin—NAD⁺ reductase), and an α3β3 oxygenase. The enzyme forms of a cis-dihydroxylated product that spontaneously rearranges to form a catechol with accompanying release of nitrite. It can typically act on many different nitroaromatic compounds, including chlorinated species. Enzymes found in different strains may have different substrate preferences. Requires Fe²⁺.

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

References:

1. Parales, J.V., Parales, R.E., Resnick, S.M. and Gibson, D.T. Enzyme specificity of 2-nitrotoluene 2,3-dioxygenase from Pseudomonas sp. strain JS42 is determined by the C-terminal region of the α subunit of the oxygenase component. J. Bacteriol. 180 (1998) 1194-1199. [PMID: 9495758]

2. Lessner, D.J., Johnson, G.R., Parales, R.E., Spain, J.C. and Gibson, D.T. Molecular characterization and substrate specificity of nitrobenzene dioxygenase from Comamonas sp. strain JS765. Appl. Environ. Microbiol. 68 (2002) 634-641. [PMID: 11823201]

3. Liu, H., Wang, S.J., Zhang, J.J., Dai, H., Tang, H. and Zhou, N.Y. Patchwork assembly of nag-like nitroarene dioxygenase genes and the 3-chlorocatechol degradation cluster for evolution of the 2-chloronitrobenzene catabolism pathway in Pseudomonas stutzeri ZWLR2-1. Appl. Environ. Microbiol. 77 (2011) 4547-4552. [PMID: 21602392]

4. Singh, D., Kumari, A., Ramaswamy, S. and Ramanathan, G. Expression, purification and substrate specificities of 3-nitrotoluene dioxygenase from Diaphorobacter sp. strain DS2. Biochem. Biophys. Res. Commun. 445 (2014) 36-42. [PMID: 24491551]

EC 1.14.12.24

Accepted name: 2,4-dinitrotoluene dioxygenase

Reaction: 2,4-dinitrotoluene + NADH + O₂ = 4-methyl-5-nitrocatechol + nitrite + NAD⁺

Other name(s): dntA (gene name)

Systematic name: 2,4-dinitrotoluene,NADH:oxygen oxidoreductase (4,5-hydroxylating, nitrite-releasing)

Comments: This enzyme, characterized from the bacterium Burkholderia sp. strain DNT, is a member of the naphthalene family of bacterial Rieske non-heme iron dioxygenases. It comprises a multicomponent system, containing a Rieske [2Fe-2S] ferredoxin, an NADH-dependent flavoprotein reductase (EC 1.18.1.3, ferredoxin—NAD⁺ reductase), and an α3β3 oxygenase. The enzyme forms a cis-dihydroxylated product that spontaneously rearranges to form a catechol with accompanying release of nitrite. It does not act on nitrobenzene. cf. EC 1.14.12.23, nitroarene dioxygenase.

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

References:

1. Suen, W.C., Haigler, B.E. and Spain, J.C. 2,4-Dinitrotoluene dioxygenase from Burkholderia sp. strain DNT: similarity to naphthalene dioxygenase. J. Bacteriol. 178 (1996) 4926-4934. [PMID: 8759857]

EC 1.14.12.25

Accepted name: p-cumate 2,3-dioxygenase

Reaction: p-cumate + NADH + H⁺ + O₂ = (2R,3S)-2,3-dihydroxy-2,3-dihydro-p-cumate + NAD⁺

For diagram of reaction click here.

Glossary: p-cumate = 4-isopropylbenzoate
(2R,3S)-2,3-dihydroxy-2,3-dihydro-p-cumate = (5S,6R)-5,6-dihydroxy-4-isopropylcyclohexa-1,3-diene-1-carboxylate

Systematic name: 4-isopropylbenzoate:oxygen 2,3-oxidoreductase

Comments: The enzyme, characterized from several Pseudomonas strains, is involved in the degradation of p-cymene and p-cumate. It comprises four components: a ferredoxin, a ferredoxin reductase, and two subunits of a catalytic component. The enzyme can also act on indole, transforming it to the water-insoluble blue dye indigo.

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

References:

1. DeFrank, J.J. and Ribbons, D.W. p-cymene pathway in Pseudomonas putida: initial reactions. J. Bacteriol. 129 (1977) 1356-1364. [PMID: 845117]

2. Wigmore, G.J. and Ribbons, D.W. p-Cymene pathway in Pseudomonas putida: selective enrichment of defective mutants by using halogenated substrate analogs. J. Bacteriol. 143 (1980) 816-824. [PMID: 7204334]

3. Eaton, R.W. and Chapman, P.J. Formation of indigo and related compounds from indolecarboxylic acids by aromatic acid-degrading bacteria: chromogenic reactions for cloning genes encoding dioxygenases that act on aromatic acids. J. Bacteriol. 177 (1995) 6983-6988. [PMID: 7592495]

4. Eaton, R.W. p-Cumate catabolic pathway in Pseudomonas putida Fl: cloning and characterization of DNA carrying the cmt operon. J. Bacteriol. 178 (1996) 1351-1362. [PMID: 8631713]

EC 1.14.12.26

Accepted name: chlorobenzene dioxygenase

Reaction: chlorobenzene + NADH + H⁺ + O₂ = (1R,2R)-3-chlorocyclohexa-3,5-diene-1,2-diol + NAD⁺

For diagram of reaction click here or click here.

Other name(s): TecA

Systematic name: chlorobenzene,NADH:oxygen oxidoreductase (1,2-hydroxylating)

Comments: This bacterial enzyme is a class IIB dioxygenase, comprising three components - a heterodimeric terminal dioxygenas, a ferredoxin protein, and a ferredoxin reductase. The enzyme acts on a range of aromatic compounds, including mono-, di-, tri-, and tetra-chlorinated benzenes and toluenes.

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

References:

1. Spiess, E., Sommer, C. and Gorisch, H. Degradation of 1,4-dichlorobenzene by Xanthobacter flavus 14p1. Appl. Environ. Microbiol. 61 (1995) 3884-3888. [PMID: 8526500]

2. Sommer, C. and Gorisch, H. Enzymology of the degradation of (di)chlorobenzenes by Xanthobacter flavus 14p1. Arch. Microbiol. 167 (1997) 384-391. [PMID: 9148781]

3. Beil, S., Happe, B., Timmis, K.N. and Pieper, D.H. Genetic and biochemical characterization of the broad spectrum chlorobenzene dioxygenase from Burkholderia sp. strain PS12 - dechlorination of 1,2,4,5-tetrachlorobenzene. Eur. J. Biochem. 247 (1997) 190-199. [PMID: 9249026]

4. Beil, S., Mason, J.R., Timmis, K.N. and Pieper, D.H. Identification of chlorobenzene dioxygenase sequence elements involved in dechlorination of 1,2,4,5-tetrachlorobenzene. J. Bacteriol. 180 (1998) 5520-5528. [PMID: 9791099]