Proposed Changes to the Enzyme List

References:

1.	Lee, A.K., Banta, A.B., Wei, J.H., Kiemle, D.J., Feng, J., Giner, J.L. and Welander, P.V. C-4 sterol demethylation enzymes distinguish bacterial and eukaryotic sterol synthesis. Proc. Natl. Acad. Sci. USA 115 (2018) 5884–5889. [PMID: 29784781]

[EC 1.1.1.417 created 2019]

1.1.1.418

Accepted name:

plant 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating)

Reaction:

a 3β-hydroxysteroid-4α-carboxylate + NAD⁺ = a 3-oxosteroid + CO₂ + NADH

For diagram of sterol ring A modification, click here

Other name(s):

3β-HSD/D1 (gene name); 3β-HSD/D2 (gene name); 3β-hydroxysteroid dehydrogenases/C-4 decarboxylase (ambiguous)

Systematic name:

3β-hydroxysteroid-4α-carboxylate:NAD⁺ 3-oxidoreductase (decarboxylating)

Comments:

The enzyme, found in plants, catalyses multiple reactions during plant sterol biosynthesis. Unlike the fungal/animal enzyme EC 1.1.1.170, 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating), the plant enzyme is specific for NAD⁺.

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 71822-23-6

References:

1.	Rondet, S., Taton, M. and Rahier, A. Identification, characterization, and partial purification of 4 α-carboxysterol-C3-dehydrogenase/ C⁴-decarboxylase from Zea mays. Arch. Biochem. Biophys. 366 (1999) 249–260. [PMID: 10356290]
2.	Rahier, A., Darnet, S., Bouvier, F., Camara, B. and Bard, M. Molecular and enzymatic characterizations of novel bifunctional 3β-hydroxysteroid dehydrogenases/C-4 decarboxylases from Arabidopsis thaliana. J. Biol. Chem. 281 (2006) 27264–27277. [PMID: 16835224]
3.	Rahier, A., Bergdoll, M., Genot, G., Bouvier, F. and Camara, B. Homology modeling and site-directed mutagenesis reveal catalytic key amino acids of 3β-hydroxysteroid-dehydrogenase/C4-decarboxylase from Arabidopsis. Plant Physiol. 149 (2009) 1872–1886. [PMID: 19218365]

[EC 1.1.1.418 created 2019]

*EC

1.2.1.30

Accepted name:

carboxylate reductase (NADP⁺)

Reaction:

an aromatic aldehyde + NADP⁺ + AMP + diphosphate = an aromatic acid + NADPH + H⁺ + ATP

Other name(s):

aromatic acid reductase; aryl-aldehyde dehydrogenase (NADP⁺)

Systematic name:

aryl-aldehyde:NADP⁺ oxidoreductase (ATP-forming)

Comments:

The enzyme contains an adenylation domain, a phosphopantetheinyl binding domain, and a reductase domain, and requires activation by attachment of a phosphopantetheinyl group. The enzyme activates its substrate to an adenylate form, followed by a transfer to the phosphopantetheinyl binding domain. The resulting thioester is subsequently transferred to the reductase domain, where it is reduced to an aldehyde and released.

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9074-94-6

References:

1.	Gross, G.G. and Zenk, M.H. Reduktion aromatischer Säuer zu Aldehyden und Alkoholen im zellfreien System. 1. Reinigung und Eigenschaften von Aryl-Aldehyd:NADP-Oxidoreduktase aus Neurospora crassa. Eur. J. Biochem. 8 (1969) 413–419. [DOI] [PMID: 4389863]
2.	Gross, G.G. Formation and reduction of intermediate acyladenylate by aryl-aldehyde. NADP oxidoreductase from Neurospora crassa. Eur. J. Biochem. 31 (1972) 585–592. [DOI] [PMID: 4405494]
3.	Venkitasubramanian, P., Daniels, L. and Rosazza, J.P. Reduction of carboxylic acids by Nocardia aldehyde oxidoreductase requires a phosphopantetheinylated enzyme. J. Biol. Chem. 282 (2007) 478–485. [PMID: 17102130]
4.	Stolterfoht, H., Schwendenwein, D., Sensen, C.W., Rudroff, F. and Winkler, M. Four distinct types of E.C. 1.2.1.30 enzymes can catalyze the reduction of carboxylic acids to aldehydes. J. Biotechnol. 257 (2017) 222–232. [PMID: 28223183]

[EC 1.2.1.30 created 1972, modified 2019]

*EC

1.3.8.6

Accepted name:

glutaryl-CoA dehydrogenase (ETF)

Reaction:

glutaryl-CoA + electron-transfer flavoprotein = crotonyl-CoA + CO₂ + reduced electron-transfer flavoprotein (overall reaction)
(1a) glutaryl-CoA + electron-transfer flavoprotein = (E)-glutaconyl-CoA + reduced electron-transfer flavoprotein
(1b) (E)-glutaconyl-CoA = crotonyl-CoA + CO₂

For diagram of Benzoyl-CoA catabolism, click here

Glossary:

(E)-glutaconyl-CoA = (2E)-4-carboxybut-2-enoyl-CoA
crotonyl-CoA = (E)-but-2-enoyl-CoA

Other name(s):

glutaryl coenzyme A dehydrogenase; glutaryl-CoA:(acceptor) 2,3-oxidoreductase (decarboxylating); glutaryl-CoA dehydrogenase

Systematic name:

glutaryl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (decarboxylating)

Comments:

Contains FAD. The enzyme catalyses the oxidation of glutaryl-CoA to glutaconyl-CoA (which remains bound to the enzyme), and the decarboxylation of the latter to crotonyl-CoA (cf. EC 7.2.4.5, glutaconyl-CoA decarboxylase). FAD is the electron acceptor in the oxidation of the substrate, and its reoxidation by electron-transfer flavoprotein completes the catalytic cycle. The anaerobic, sulfate-reducing bacterium Desulfococcus multivorans contains two glutaryl-CoA dehydrogenases: a decarboxylating enzyme (this entry), and a non-decarboxylating enzyme that only catalyses the oxidation to glutaconyl-CoA [EC 1.3.99.32, glutaryl-CoA dehydrogenase (acceptor)].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37255-38-2

References:

1.	Besrat, A., Polan, C.E. and Henderson, L.M. Mammalian metabolism of glutaric acid. J. Biol. Chem. 244 (1969) 1461–1467. [PMID: 4304226]
2.	Hartel, U., Eckel, E., Koch, J., Fuchs, G., Linder, D. and Buckel, W. Purification of glutaryl-CoA dehydrogenase from Pseudomonas sp., an enzyme involved in the anaerobic degradation of benzoate. Arch. Microbiol. 159 (1993) 174–181. [PMID: 8439237]
3.	Dwyer, T.M., Zhang, L., Muller, M., Marrugo, F. and Frerman, F. The functions of the flavin contact residues, αArg²⁴⁹ and βTyr¹⁶, in human electron transfer flavoprotein. Biochim. Biophys. Acta 1433 (1999) 139–152. [DOI] [PMID: 10446367]
4.	Rao, K.S., Albro, M., Dwyer, T.M. and Frerman, F.E. Kinetic mechanism of glutaryl-CoA dehydrogenase. Biochemistry 45 (2006) 15853–15861. [DOI] [PMID: 17176108]

[EC 1.3.8.6 created 1972 as EC 1.3.99.7, transferred 2012 to EC 1.3.8.6, modified 2013, modified 2019]

*EC

1.4.1.14

Accepted name:

glutamate synthase (NADH)

Reaction:

2 L-glutamate + NAD⁺ = L-glutamine + 2-oxoglutarate + NADH + H⁺
(1a) L-glutamate + NH₃ = L-glutamine + H₂O
(1b) L-glutamate + NAD⁺ + H₂O = NH₃ + 2-oxoglutarate + NADH + H⁺

For diagram of glutamic acid biosynthesis, click here

Other name(s):

glutamate (reduced nicotinamide adenine dinucleotide) synthase; NADH: GOGAT; L-glutamate synthase (NADH); L-glutamate synthetase; NADH-glutamate synthase; NADH-dependent glutamate synthase

Systematic name:

L-glutamate:NAD⁺ oxidoreductase (transaminating)

Comments:

A flavoprotein (FMN). The reaction takes place in the direction of L-glutamate production. The protein is composed of two domains, one hydrolysing L-glutamine to NH₃ and L-glutamate (cf. EC 3.5.1.2, glutaminase), the other combining the produced NH₃ with 2-oxoglutarate to produce a second molecule of L-glutamate (cf. EC 1.4.1.2, glutamate dehydrogenase).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 65589-88-0

References:

1.	Roon, R.J., Even, H.L. and Larimore, F. Glutamate synthase: properties of the reduced nicotinamide adenine dinucleotide-dependent enzyme from Saccharomyces cerevisiae. J. Bacteriol. 118 (1974) 89–95. [PMID: 4362465]
2.	Boland, M.J. and Benny, A.G. Enzymes of nitrogen metabolism in legume nodules. Purification and properties of NADH-dependent glutamate synthase from lupin nodules. Eur. J. Biochem. 79 (1977) 355–362. [DOI] [PMID: 21790]
3.	Masters, D.S., Jr. and Meister, A. Inhibition of homocysteine sulfonamide of glutamate synthase purified from Saccharomyces cerevisiae. J. Biol. Chem. 257 (1982) 8711–8715. [PMID: 7047525]
4.	Anderson, M.P., Vance, C.P., Heichel, G.H. and Miller, S.S. Purification and characterization of NADH-glutamate synthase from alfalfa root nodules. Plant Physiol. 90 (1989) 351–358. [PMID: 16666762]
5.	Blanco, L., Reddy, P.M., Silvente, S., Bucciarelli, B., Khandual, S., Alvarado-Affantranger, X., Sanchez, F., Miller, S., Vance, C. and Lara-Flores, M. Molecular cloning, characterization and regulation of two different NADH-glutamate synthase cDNAs in bean nodules. Plant Cell Environ. 31 (2008) 454–472. [PMID: 18182018]

[EC 1.4.1.14 created 1978, modified 2019]

*EC

1.8.5.3

Accepted name:

respiratory dimethylsulfoxide reductase

Reaction:

dimethylsulfide + menaquinone + H₂O = dimethylsulfoxide + menaquinol

For diagram of dimethyl sulfide catabolism, click here

Other name(s):

dmsABC (gene names); DMSO reductase (ambiguous); dimethylsulfoxide reductase (ambiguous)

Systematic name:

dimethyl sulfide:menaquinone oxidoreductase

Comments:

The enzyme participates in bacterial electron transfer pathways in which dimethylsulfoxide (DMSO) is the terminal electron acceptor. It is composed of three subunits - DmsA contains a bis(guanylyl molybdopterin) cofactor and a [4Fe-4S] cluster, DmsB is an iron-sulfur protein, and DmsC is a transmembrane protein that anchors the enzyme and accepts electrons from the quinol pool. The electrons are passed through DmsB to DmsA and on to DMSO. The enzyme can also reduce pyridine-N-oxide and trimethylamine N-oxide to the corresponding amines with lower activity.

Links to other databases:

References:

1.	Daruwala, R. and Meganathan, R. Dimethyl sulfoxide reductase is not required for trimethylamine N-oxide reduction in Escherichia coli. FEMS Microbiol. Lett. 67 (1991) 255–259. [PMID: 1769531]
2.	Miguel, L. and Meganthan, R. Electron donors and the quinone involved in dimethyl sulfoxide reduction in Escherichia coli. Curr. Microbiol. 22 (1991) 109–115.
3.	Simala-Grant, J.L. and Weiner, J.H. Kinetic analysis and substrate specificity of Escherichia coli dimethyl sulfoxide reductase. Microbiology 142 (1996) 3231–3239. [DOI] [PMID: 8969520]
4.	Rothery, R.A., Trieber, C.A. and Weiner, J.H. Interactions between the molybdenum cofactor and iron-sulfur clusters of Escherichia coli dimethylsulfoxide reductase. J. Biol. Chem. 274 (1999) 13002–13009. [DOI] [PMID: 10224050]

[EC 1.8.5.3 created 2011, modified 2019]

1.13.11.88

Accepted name:

isoeugenol monooxygenase

Reaction:

isoeugenol + O₂ = vanillin + acetaldehyde

For diagram of anethole, chavicol, eugenol and isoeugenol biosynthesis, click here

Glossary:

isoeugenol = 2-methoxy-4-(prop-1-en-1-yl)phenol

Other name(s):

iem (gene name)

Systematic name:

isoeugenol:oxygen 7,8-oxidoreductase (bond-cleaving)

Comments:

Contains iron(II). The enzyme, charcterised from the bacteria Pseudomonas putida and Pseudomonas nitroreducens, catalyses the epoxidation of the double bond in the side chain of isoeugenol, followed by a second oxygenation and cleavage of the side chain in the form of acetaldehyde.

Links to other databases:

References:

1.	Shimoni, E., Ravid, U. and Shoham, Y. Isolation of a Bacillus sp. capable of transforming isoeugenol to vanillin. J. Biotechnol. 78 (2000) 1–9. [PMID: 10702906]
2.	Yamada, M., Okada, Y., Yoshida, T. and Nagasawa, T. Biotransformation of isoeugenol to vanillin by Pseudomonas putida IE27 cells. Appl. Microbiol. Biotechnol. 73 (2007) 1025–1030. [PMID: 16944125]
3.	Yamada, M., Okada, Y., Yoshida, T. and Nagasawa, T. Purification, characterization and gene cloning of isoeugenol-degrading enzyme from Pseudomonas putida IE27. Arch. Microbiol. 187 (2007) 511–517. [PMID: 17516050]
4.	Ryu, J.Y., Seo, J., Unno, T., Ahn, J.H., Yan, T., Sadowsky, M.J. and Hur, H.G. Isoeugenol monooxygenase and its putative regulatory gene are located in the eugenol metabolic gene cluster in Pseudomonas nitroreducens Jin1. Arch. Microbiol. 192 (2010) 201–209. [PMID: 20091296]
5.	Ryu, J.Y., Seo, J., Park, S., Ahn, J.H., Chong, Y., Sadowsky, M.J. and Hur, H.G. Characterization of an isoeugenol monooxygenase (iem) from Pseudomonas nitroreducens Jin1 that transforms isoeugenol to vanillin. Biosci. Biotechnol. Biochem. 77 (2013) 289–294. [PMID: 23391906]

[EC 1.13.11.88 created 2019]

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:

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. [DOI] [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 1.14.11.61 created 2019]

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 vanillin biosynthesis, 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:

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. [DOI] [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 1.14.11.62 created 2019]

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:

References:

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 1.14.11.63 created 2019]

1.14.13.243

Accepted name:

toluene 2-monooxygenase

Reaction:

(1) toluene + NADH + H⁺ + O₂ = 2-methylphenol + NAD⁺ + H₂O
(2) 2-methylphenol + NADH + H⁺ + O₂ = 3-methylcatechol + NAD⁺ + H₂O

Other name(s):

tomA1/2/3/4/5 (gene names); toluene ortho-monooxygenase

Systematic name:

toluene,NADH:oxygen oxidoreductase (2,3-dihydroxylating)

Comments:

The enzyme, characterized from the bacterium Burkholderia cepacia, belongs to a class of nonheme, oxygen-dependent diiron enzymes. It contains a hydroxylase component with two binuclear iron centers, an NADH-oxidoreductase component containing FAD and a [2Fe-2S] iron-sulfur cluster, and a third component involved in electron transfer between the hydroxylase and the reductase. The enzyme dihydroxylates its substrate in two sequential hydroxylations, initially forming 2-methylphenol, which is hydroxylated to 3-methylcatechol.

Links to other databases:

References:

1.	Newman, L.M. and Wackett, L.P. Purification and characterization of toluene 2-monooxygenase from Burkholderia cepacia G4. Biochemistry 34 (1995) 14066–14076. [PMID: 7578004]
2.	Yeager, C.M., Bottomley, P.J., Arp, D.J. and Hyman, M.R. Inactivation of toluene 2-monooxygenase in Burkholderia cepacia G4 by alkynes. Appl. Environ. Microbiol. 65 (1999) 632–639. [PMID: 9925593]
3.	Canada, K.A., Iwashita, S., Shim, H. and Wood, T.K. Directed evolution of toluene ortho-monooxygenase for enhanced 1-naphthol synthesis and chlorinated ethene degradation. J. Bacteriol. 184 (2002) 344–349. [PMID: 11751810]

[EC 1.14.13.243 created 2019]

1.14.13.244

Accepted name:

phenol 2-monooxygenase (NADH)

Reaction:

phenol + NADH + H⁺ + O₂ = catechol + NAD⁺ + H₂O

For diagram of catechol biosynthesis, click here

Other name(s):

dmpLMNOP (gene names)

Systematic name:

phenol,NADH:oxygen oxidoreductase (2-hydroxylating)

Comments:

The enzyme, characterized from the bacteria Pseudomonas sp. CF600 and Acinetobacter radioresistens, consists of a multisubunit oxygenease component that contains the active site and a dinuclear iron center, a reductase component that contains FAD and one iron-sulfur cluster, and a regulatory component. The reductase component is responsible for transferring electrons from NADH to the dinuclear iron center.

Links to other databases:

References:

1.	Nordlund, I., Powlowski, J. and Shingler, V. Complete nucleotide sequence and polypeptide analysis of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600. J. Bacteriol. 172 (1990) 6826–6833. [PMID: 2254258]
2.	Powlowski, J. and Shingler, V. In vitro analysis of polypeptide requirements of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600. J. Bacteriol. 172 (1990) 6834–6840. [PMID: 2254259]
3.	Powlowski, J., Sealy, J., Shingler, V. and Cadieux, E. On the role of DmpK, an auxiliary protein associated with multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600. J. Biol. Chem. 272 (1997) 945–951. [PMID: 8995386]
4.	Qian, H., Edlund, U., Powlowski, J., Shingler, V. and Sethson, I. Solution structure of phenol hydroxylase protein component P2 determined by NMR spectroscopy. Biochemistry 36 (1997) 495–504. [PMID: 9012665]
5.	Cadieux, E., Vrajmasu, V., Achim, C., Powlowski, J. and Munck, E. Biochemical, Mossbauer, and EPR studies of the diiron cluster of phenol hydroxylase from Pseudomonas sp. strain CF 600. Biochemistry 41 (2002) 10680–10691. [PMID: 12186554]

[EC 1.14.13.244 created 2019]

1.14.13.245

Accepted name:

assimilatory dimethylsulfide S-monooxygenase

Reaction:

(1) dimethyl sulfide + NADH + H⁺ + O₂ = dimethyl sulfoxide + NAD⁺ + H₂O
(2) dimethyl sulfoxide + NADH + H⁺ + O₂ = dimethyl sulfone + NAD⁺ + H₂O

For diagram of dimethyl sulfide catabolism, click here

Other name(s):

dsoBCDEF (gene names)

Systematic name:

dimethyl sulfide,NADH:oxygen oxidoreductase (S-oxidizing)

Comments:

The enzyme, studied from the bacterium Acinetobacter sp. strain 20B, is very similar to EC 1.14.13.244, phenol 2-monooxygenase (NADH). It consists of a multisubunit oxygenease component that contains the active site and a dinuclear iron center, a reductase component that contains FAD and one iron-sulfur cluster, and a regulatory component. The three components comprise five different polypeptides. The enzyme catalyses the first two steps of a dimethyl sulfide oxidation pathway in this organism.

Links to other databases:

References:

1.	Horinouchi, M., Kasuga, K., Nojiri, H., Yamane, H. and Omori, T. Cloning and characterization of genes encoding an enzyme which oxidizes dimethyl sulfide in Acinetobacter sp. strain 20B. FEMS Microbiol. Lett. 155 (1997) 99–105. [PMID: 9345770]
2.	Horinouchi, M., Yoshida, T., Nojiri, H., Yamane, H. and Omori, T. Polypeptide requirement of multicomponent monooxygenase DsoABCDEF for dimethyl sulfide oxidizing activity. Biosci. Biotechnol. Biochem. 63 (1999) 1765–1771. [PMID: 26300166]

[EC 1.14.13.245 created 2019]

1.14.13.246

Accepted name:

4β-methylsterol monooxygenase

Reaction:

a 3β-hydroxy-4,4-dimethylsteroid + 3 NADH + 3 H⁺ + 3 O₂ = a 3β-hydroxy-4α-methylsteroid-4β-carboxylate + 3 NAD⁺ + 4 H₂O (overall reaction)
(1a) a 3β-hydroxy-4,4-dimethylsteroid + NADH + H⁺ + O₂ = a 3β-hydroxy-4β-hydroxymethyl-4α-methylsteroid + NAD⁺ + H₂O
(1b) a 3β-hydroxy-4β-hydroxymethyl-4α-methylsteroid + NADH + H⁺ + O₂ = a 3β-hydroxy-4β-formyl-4α-methylsteroid + NAD⁺ + 2 H₂O
(1c) a 3β-hydroxy-4β-formyl-4α-methylsteroid + NADH + H⁺ + O₂ = a 3β-hydroxy-4α-methylsteroid-4β-carboxylate + NAD⁺ + H₂O

Other name(s):

sdmA (gene name)

Systematic name:

3β-hydroxy-4,4-dimethylsteroid,NADH:oxygen oxidoreductase (C-4mβ-hydroxylating)

Comments:

Contains a Rieske [2Fe-2S] iron-sulfur cluster. This bacterial enzyme (SdmA) participates in the biosynthesis of bacterial sterols. Together with SdmB it forms an enzyme system that removes one methyl group from the C-4 position of 4,4-dimethylated steroid molecules. SdmA catalyses three successive oxidations of the C-4β methyl group, turning it into a carboxylate group; the second enzyme, SdmB, is a bifunctional enzyme that catalyses two different activities. As EC 1.1.1.417, 3β-hydroxysteroid-4β-carboxylate 3-dehydrogenase (decarboxylating), it catalyses an oxidative decarboxylation that results in reduction of the 3β-hydroxy group at the C-3 carbon to an oxo group. As EC 1.1.1.270, 3β-hydroxysteroid 3-dehydrogenase, it reduces the 3-oxo group back to a 3β-hydroxyl. Unlike the animal/fungal enzyme EC 1.14.18.9, 4α-methylsterol monooxygenase, and the plant enzymes EC 1.14.18.10, plant 4,4-dimethylsterol C-4α-methyl-monooxygenase, and EC 1.14.18.11, plant 4α-monomethylsterol monooxygenase, this enzyme acts preferentially on the 4β-methyl group. Since no epimerization of the remaining C-4α methyl group occurs, the enzyme can only remove one methyl group, leaving a 4α-monomethylated product. Known substrates include 4,4-dimethyl-5α-cholest-8-en-3β-ol and 14-demethyllanosterol.

Links to other databases:

References:

1.	Lee, A.K., Banta, A.B., Wei, J.H., Kiemle, D.J., Feng, J., Giner, J.L. and Welander, P.V. C-4 sterol demethylation enzymes distinguish bacterial and eukaryotic sterol synthesis. Proc. Natl. Acad. Sci. USA 115 (2018) 5884–5889. [PMID: 29784781]

[EC 1.14.13.246 created 2019]

1.14.14.171

Accepted name:

β-amyrin 16α-hydroxylase

Reaction:

β-amyrin + [reduced NADPH—hemoprotein reductase] + O₂ = 16α-hydroxy-β-amyrin + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of hydroxy-β-amyrin biosynthesis, click here

Glossary:

16α-hydroxy-β-amyrin = olean-12-ene-3β,16α-diol

Other name(s):

CYP87D16

Systematic name:

β-amyrin,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (16α-hydroxylating)

Comments:

A cytochrome P-450 (heme-thiolate) protein isolated from the plant Maesa lanceolata (false assegai). Involved in the biosynthesis of maesasaponins. It also acts on some derivatives of β-amyrin such as erythrodiol or oleanolic acid.

Links to other databases:

References:

1.	Moses, T., Pollier, J., Almagro, L., Buyst, D., Van Montagu, M., Pedreño, M.A., Martins, J.C., Thevelein, J.M. and Goossens, A. Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum. Proc. Natl. Acad. Sci. USA 111 (2014) 1634–1639. [PMID: 24434554]
2.	Moses, T., Pollier, J., Faizal, A., Apers, S., Pieters, L., Thevelein, J.M., Geelen, D. and Goossens, A. Unraveling the triterpenoid saponin biosynthesis of the African shrub Maesa lanceolata. Mol. Plant 8 (2015) 122–135. [DOI] [PMID: 25578277]

[EC 1.14.14.171 created 2019]

1.14.15.36

Accepted name:

sterol 14α-demethylase (ferredoxin)

Reaction:

a 14α-methylsteroid + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H⁺ + 3 O₂ = a Δ¹⁴-steroid + formate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H₂O (overall reaction)
(1a) a 14α-methylsteroid + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = a 14α-hydroxymethylsteroid + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(1b) a 14α-hydroxymethylsteroid + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = a 14α-formylsteroid + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H₂O
(1c) a 14α-formylsteroid + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = a Δ¹⁴-steroid + formate + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O

Other name(s):

cyp51 (gene name)

Systematic name:

sterol,reduced ferredoxin:oxygen oxidoreductase (14-methyl cleaving)

Comments:

A cytochrome P-450 (heme-thiolate) protein found in several bacterial species. The enzyme, which is involved in sterol biosynthesis, catalyses a hydroxylation and a reduction of the 14α-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond. The enzyme from Methylococcus capsulatus is fused to the ferredoxin by an alanine-rich linker. cf. EC 1.14.14.154, sterol 14α-demethylase.

Links to other databases:

References:

1.	Jackson, C.J., Lamb, D.C., Marczylo, T.H., Warrilow, A.G., Manning, N.J., Lowe, D.J., Kelly, D.E. and Kelly, S.L. A novel sterol 14α-demethylase/ferredoxin fusion protein (MCCYP51FX) from Methylococcus capsulatus represents a new class of the cytochrome P450 superfamily. J. Biol. Chem. 277 (2002) 46959–46965. [PMID: 12235134]
2.	Rezen, T., Debeljak, N., Kordis, D. and Rozman, D. New aspects on lanosterol 14α-demethylase and cytochrome P450 evolution: lanosterol/cycloartenol diversification and lateral transfer. J. Mol. Evol. 59 (2004) 51–58. [PMID: 15383907]
3.	Desmond, E. and Gribaldo, S. Phylogenomics of sterol synthesis: insights into the origin, evolution, and diversity of a key eukaryotic feature. Genome Biol Evol 1 (2009) 364–381. [PMID: 20333205]

[EC 1.14.15.36 created 2019]

1.14.15.37

Accepted name:

luteothin monooxygenase

Reaction:

luteothin + 2 O₂ + 4 reduced ferredoxin [iron-sulfur] cluster + 4 H⁺ = aureothin + 3 H₂O + 4 oxidized ferredoxin [iron-sulfur] cluster (overall reaction)
(1a) luteothin + O₂ + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ = (7R)-7-hydroxyluteothin + H₂O + 2 oxidized ferredoxin [iron-sulfur] cluster
(1b) (7R)-7-hydroxyluteothin + O₂ + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ = aureothin + 2 H₂O + 2 oxidized ferredoxin [iron-sulfur] cluster

For diagram of aureothin catabolism, click here

Glossary:

luteothin = 2-[(3E,5E)-3,5-dimethyl-6-(4-nitrophenyl)hexa-3,5-dien-1-yl]-6-methoxy-3,5-dimethyl-4H-pyran-4-one
aureothin = 2-methoxy-3,5-dimethyl-6-[(2R,4Z)-4-[(2E)-2-methyl-3-(4-nitrophenyl)prop-2-en-1-ylidene]oxolan-2-yl]-4H-pyran-4-one
spectinabilin = neoaureothin = 2-methoxy-3,5-dimethyl-6-[(2R,4Z)-4-[(2E,4E,6E)-2,4,6-trimethyl-7-(4-nitrophenyl)hepta-2,4,6-trien-1-ylidene]oxolan-2-yl]-4H-pyran-4-one

Other name(s):

aurH (gene name)

Systematic name:

luteothin,ferredoxin:oxygen oxidoreductase (aureothin-forming)

Comments:

The enzyme, characterized from the bacterium Streptomyces thioluteus, is a bifunctional cytochrome P-450 (heme-thiolate) protein that catalyses both the hydroxylation of its substrate and formation of a furan ring, the final step in the biosynthesis of the antibiotic aureothin. In the bacteria Streptomyces orinoci and Streptomyces spectabilis an orthologous enzyme catalyses a similar reaction that forms spectinabilin.

Links to other databases:

References:

1.	He, J., Muller, M. and Hertweck, C. Formation of the aureothin tetrahydrofuran ring by a bifunctional cytochrome P450 monooxygenase. J. Am. Chem. Soc. 126 (2004) 16742–16743. [PMID: 15612710]
2.	Traitcheva, N., Jenke-Kodama, H., He, J., Dittmann, E. and Hertweck, C. Non-colinear polyketide biosynthesis in the aureothin and neoaureothin pathways: an evolutionary perspective. ChemBioChem 8 (2007) 1841–1849. [PMID: 17763486]

[EC 1.14.15.37 created 2019]

*EC

1.14.18.9

Accepted name:

4α-methylsterol monooxygenase

Reaction:

4,4-dimethyl-5α-cholest-7-en-3β-ol + 6 ferrocytochrome b₅ + 3 O₂ + 6 H⁺ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 6 ferricytochrome b₅ + 4 H₂O (overall reaction)
(1a) 4,4-dimethyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 4α-hydroxymethyl-4β-methyl-5α-cholest-7-en-3β-ol + 2 ferricytochrome b₅ + H₂O
(1b) 4α-hydroxymethyl-4β-methyl-5α-cholest-7-en-3β-ol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferricytochrome b₅ + 2 H₂O
(1c) 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carbaldehyde + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 3β-hydroxy-4β-methyl-5α-cholest-7-ene-4α-carboxylate + 2 ferricytochrome b₅ + H₂O

For diagram of sterol ring A modification, click here

Other name(s):

methylsterol hydroxylase (ambiguous); 4-methylsterol oxidase (ambiguous); 4,4-dimethyl-5α-cholest-7-en-3β-ol,hydrogen-donor:oxygen oxidoreductase (hydroxylating) (ambiguous); methylsterol monooxygenase (ambiguous); ERG25 (gene name); MSMO1 (gene name); 4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b₅:oxygen oxidoreductase (hydroxylating) (ambiguous)

Systematic name:

4,4-dimethyl-5α-cholest-7-en-3β-ol,ferrocytochrome-b₅:oxygen oxidoreductase (C4α-methyl-hydroxylating)

Comments:

This enzyme is found in fungi and animals and catalyses a step in the biosynthesis of important sterol molecules such as ergosterol and cholesterol, respectively. The enzyme acts on the 4α-methyl group. Subsequent decarboxylation by EC 1.1.1.170, 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating), occurs concomitantly with epimerization of the remaining 4β-methyl into the 4α position, thus making it a suitable substrate for a second round of catalysis. cf. EC 1.14.13.246, 4β-methylsterol monooxygenase; EC 1.14.18.10, plant 4,4-dimethylsterol C-4α-methyl-monooxygenase; and EC 1.14.18.11, plant 4α-monomethylsterol monooxygenase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 37256-80-7

References:

1.	Miller, W.L., Kalafer, M.E., Gaylor, J.L. and Delwicke, C.V. Investigation of the component reactions of oxidative sterol demethylation. Study of the aerobic and anaerobic processes. Biochemistry 6 (1967) 2673–2678. [PMID: 4383278]
2.	Gaylor, J.L. and Mason, H.S. Investigation of the component reactions of oxidative sterol demethylation. Evidence against participation of cytochrome P-450. J. Biol. Chem. 243 (1968) 4966–4972. [PMID: 4234469]
3.	Sharpless, K.B., Snyder, T.E., Spencer, T.A., Maheshwari, K.K. and Nelson, J.A. Biological demethylation of 4,4-dimethyl sterols, Evidence for enzymic epimerization of the 4β-methyl group prior to its oxidative removal. J. Am. Chem. Soc. 91 (1969) 3394–3396. [PMID: 5791927]
4.	Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624–10629. [PMID: 7430141]
5.	Fukushima, H., Grinstead, G.F. and Gaylor, J.L. Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b₅-dependence of 4-methyl sterol oxidase. J. Biol. Chem. 256 (1981) 4822–4826. [PMID: 7228857]
6.	Kawata, S., Trzaskos, J.M. and Gaylor, J.L. Affinity chromatography of microsomal enzymes on immobilized detergent-solubilized cytochrome b₅. J. Biol. Chem. 261 (1986) 3790–3799. [PMID: 3949790]

[EC 1.14.18.9 created 1972 as EC 1.14.99.16, transferred 2002 to EC 1.14.13.72, transferred 2017 to EC 1.14.18.9, modified 2019]

1.14.18.10

Accepted name:

plant 4,4-dimethylsterol C-4α-methyl-monooxygenase

Reaction:

24-methylidenecycloartanol + 6 ferrocytochrome b₅ + 3 O₂ + 6 H⁺ = 3β-hydroxy-4β,14α-dimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-4α-carboxylate + 6 ferricytochrome b₅ + 4 H₂O (overall reaction)
(1a) 24-methylidenecycloartanol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 4α-(hydroxymethyl)-4β,14α-dimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-3β-ol + 2 ferricytochrome b₅ + H₂O
(1b) 4α-(hydroxymethyl)-4β,14α-dimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-3β-ol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 4α-formyl-4β,14α-dimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-3β-ol + 2 ferricytochrome b₅ + 2 H₂O
(1c) 4α-formyl-4β,14α-dimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-3β-ol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 3β-hydroxy-4β,14α-dimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-4α-carboxylate + 2 ferricytochrome b₅ + H₂O

Glossary:

24-methylidenecycloartanol = 4α,4β,14α-trimethyl-9β,19-cyclo-5α-ergost-24(24¹)-en-3β-ol

Other name(s):

SMO1 (gene name)

Systematic name:

24-methylidenecycloartanol,ferrocytochrome-b₅:oxygen oxidoreductase (C-4α-methyl-hydroxylating)

Comments:

This plant enzyme catalyses a step in the biosynthesis of sterols. It acts on the 4α-methyl group of the 4,4-dimethylated intermediate 24-methylidenecycloartanol and catalyses three successive oxidations, turning it into a carboxyl group. The carboxylate is subsequently removed by EC 1.1.1.418, plant 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating), which also catalyses the epimerization of the remaining 4β-methyl into the 4α position. Unlike the fungal/animal enzyme EC 1.14.18.9, 4α-methylsterol monooxygenase, this enzyme is not able to remove the methyl group from C-4-monomethylated substrates. That activity is performed in plants by a second enzyme, EC 1.14.18.11, plant 4α-monomethylsterol monooxygenase.

Links to other databases:

References:

1.	Pascal, S., Taton, M. and Rahier, A. Plant sterol biosynthesis. Identification and characterization of two distinct microsomal oxidative enzymatic systems involved in sterol C4-demethylation. J. Biol. Chem. 268 (1993) 11639–11654. [PMID: 8505296]
2.	Rahier, A., Smith, M. and Taton, M. The role of cytochrome b₅ in 4α-methyl-oxidation and C5(6) desaturation of plant sterol precursors. Biochem. Biophys. Res. Commun. 236 (1997) 434–437. [DOI] [PMID: 9240456]
3.	Darnet, S., Bard, M. and Rahier, A. Functional identification of sterol-4α-methyl oxidase cDNAs from Arabidopsis thaliana by complementation of a yeast erg25 mutant lacking sterol-4α-methyl oxidation. FEBS Lett. 508 (2001) 39–43. [PMID: 11707264]
4.	Darnet, S. and Rahier, A. Plant sterol biosynthesis: identification of two distinct families of sterol 4α-methyl oxidases. Biochem. J. 378 (2004) 889–898. [PMID: 14653780]

[EC 1.14.18.10 created 2019]

1.14.18.11

Accepted name:

plant 4α-monomethylsterol monooxygenase

Reaction:

24-methylidenelophenol + 6 ferrocytochrome b₅ + 3 O₂ + 6 H⁺ = 3β-hydroxyergosta-7,24(24¹)-dien-4α-carboxylate + 6 ferricytochrome b₅ + 4 H₂O (overall reaction)
(1a) 24-methylidenelophenol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 4α-(hydroxymethyl)ergosta-7,24(24¹)-dien-3β-ol + 2 ferricytochrome b₅ + H₂O
(1b) 4α-(hydroxymethyl)ergosta-7,24(24¹)-dien-3β-ol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 4α-formylergosta-7,24(24¹)-dien-3β-ol + 2 ferricytochrome b₅ + 2 H₂O
(1c) 4α-formylergosta-7,24(24¹)-dien-3β-ol + 2 ferrocytochrome b₅ + O₂ + 2 H⁺ = 3β-hydroxyergosta-7,24(24¹)-dien-4α-carboxylate + 2 ferricytochrome b₅ + H₂O

Glossary:

24-methylidenelophenol = 4α-methyl-5α-ergosta-7,24-dien-3β-ol

Other name(s):

SMO2 (gene name)

Systematic name:

24-ethylidenelophenol,ferrocytochrome-b₅:oxygen oxidoreductase (C-4α-methyl-hydroxylating)

Comments:

This plant enzyme catalyses a step in the biosynthesis of sterols. It acts on the methyl group of the 4α-methylated intermediates 24-ethylidenelophenol and 24-methylidenelophenol and catalyses three successive oxidations, turning it into a carboxyl group. The carboxylate is subsequently removed by EC 1.1.1.418, plant 3β-hydroxysteroid-4α-carboxylate 3-dehydrogenase (decarboxylating). Unlike the fungal/animal enzyme EC 1.14.18.9, 4α-methylsterol monooxygenase, this enzyme is not able to act on 4,4-dimethylated substrates. That activity, which occurs earlier in the pathway, is performed in plants by a second enzyme, EC 1.14.18.10, plant 4,4-dimethylsterol C-4α-methyl-monooxygenase.

Links to other databases:

References:

1.	Pascal, S., Taton, M. and Rahier, A. Plant sterol biosynthesis. Identification and characterization of two distinct microsomal oxidative enzymatic systems involved in sterol C4-demethylation. J. Biol. Chem. 268 (1993) 11639–11654. [PMID: 8505296]
2.	Rahier, A., Smith, M. and Taton, M. The role of cytochrome b₅ in 4α-methyl-oxidation and C5(6) desaturation of plant sterol precursors. Biochem. Biophys. Res. Commun. 236 (1997) 434–437. [DOI] [PMID: 9240456]
3.	Darnet, S., Bard, M. and Rahier, A. Functional identification of sterol-4α-methyl oxidase cDNAs from Arabidopsis thaliana by complementation of a yeast erg25 mutant lacking sterol-4α-methyl oxidation. FEBS Lett. 508 (2001) 39–43. [PMID: 11707264]
4.	Darnet, S. and Rahier, A. Plant sterol biosynthesis: identification of two distinct families of sterol 4α-methyl oxidases. Biochem. J. 378 (2004) 889–898. [PMID: 14653780]

[EC 1.14.18.11 created 2019]

1.14.99.65

Accepted name:

4-amino-L-phenylalanyl-[CmlP-peptidyl-carrier-protein] 3-hydroxylase

Reaction:

4-amino-L-phenylalanyl-[CmlP-peptidyl-carrier-protein] + reduced acceptor + O₂ = 2-(4-aminophenyl)-L-seryl-[CmlP-peptidyl-carrier-protein] + acceptor + H₂O

Other name(s):

cmlA (gene name)

Systematic name:

4-amino-L-phenylalanyl-[CmlP-peptidyl-carrier-protein],acceptor:oxygen 3-oxidoreductase

Comments:

The enzyme, characterized from the bacterium Streptomyces venezuelae, participates in the biosynthesis of the antibiotic chloramphenicol. It carries an oxygen-bridged dinuclear iron cluster. The native electron donor remains unknown, and the enzyme was assayed in vitro using sodium dithionite. The enzyme only acts on its substrate when it is loaded onto the peptidyl-carrier domain of the CmlP non-ribosomal peptide synthase.

Links to other databases:

References:

1.	Makris, T.M., Chakrabarti, M., Munck, E. and Lipscomb, J.D. A family of diiron monooxygenases catalyzing amino acid β-hydroxylation in antibiotic biosynthesis. Proc. Natl. Acad. Sci. USA 107 (2010) 15391–15396. [PMID: 20713732]

[EC 1.14.99.65 created 2019]

*EC

1.20.4.1

Accepted name:

arsenate reductase (glutathione/glutaredoxin)

Reaction:

arsenate + glutathione + glutaredoxin = arsenite + a glutaredoxin-glutathione disulfide + H₂O

For diagram of arsenate catabolism, click here

Other name(s):

ArsC (ambiguous); arsenate:glutaredoxin oxidoreductase; arsenate reductase (glutaredoxin)

Systematic name:

arsenate:glutathione/glutaredoxin oxidoreductase

Comments:

The enzyme is part of a system for detoxifying arsenate. The substrate binds to a catalytic cysteine residue, forming a covalent thiolate—As(V) intermediate. A tertiary intermediate is then formed between the arsenic, the enzyme’s cysteine, and a glutathione cysteine. This intermediate is reduced by glutaredoxin, which forms a dithiol with the glutathione, leading to the dissociation of arsenite. Thus reduction of As(V) is mediated by three cysteine residues: one in ArsC, one in glutathione, and one in glutaredoxin. Although the arsenite formed is more toxic than arsenate, it can be extruded from some bacteria by EC 7.3.2.7, arsenite-transporting ATPase; in other organisms, arsenite can be methylated by EC 2.1.1.137, arsenite methyltransferase, in a pathway that produces non-toxic organoarsenical compounds. cf. EC 1.20.4.4, arsenate reductase (thioredoxin).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 146907-46-2

References:

1.	Gladysheva, T., Liu, J.Y. and Rosen, B.P. His-8 lowers the pKa of the essential Cys-12 residue of the ArsC arsenate reductase of plasmid R773. J. Biol. Chem. 271 (1996) 33256–33260. [DOI] [PMID: 8969183]
2.	Gladysheva, T.B., Oden, K.L. and Rosen, B.P. Properties of the arsenate reductase of plasmid R773. Biochemistry 33 (1994) 7288–7293. [PMID: 8003492]
3.	Holmgren, A. and Aslund, F. Glutaredoxin. Methods Enzymol. 252 (1995) 283–292. [DOI] [PMID: 7476363]
4.	Krafft, T. and Macy, J.M. Purification and characterization of the respiratory arsenate reductase of Chrysiogenes arsenatis. Eur. J. Biochem. 255 (1998) 647–653. [DOI] [PMID: 9738904]
5.	Martin, J.L. Thioredoxin - a fold for all reasons. Structure 3 (1995) 245–250. [DOI] [PMID: 7788290]
6.	Radabaugh, T.R. and Aposhian, H.V. Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase. Chem. Res. Toxicol. 13 (2000) 26–30. [DOI] [PMID: 10649963]
7.	Sato, T. and Kobayashi, Y. The ars operon in the skin element of Bacillus subtilis confers resistance to arsenate and arsenite. J. Bacteriol. 180 (1998) 1655–1661. [PMID: 9537360]
8.	Shi, J., Vlamis-Gardikas, V., Aslund, F., Holmgren, A. and Rosen, B.P. Reactivity of glutaredoxins 1, 2, and 3 from Escherichia coli shows that glutaredoxin 2 is the primary hydrogen donor to ArsC-catalyzed arsenate reduction. J. Biol. Chem. 274 (1999) 36039–36042. [DOI] [PMID: 10593884]
9.	Mukhopadhyay, R. and Rosen, B.P. Arsenate reductases in prokaryotes and eukaryotes. Environ Health Perspect 110 Suppl 5 (2002) 745–748. [PMID: 12426124]
10.	Messens, J. and Silver, S. Arsenate reduction: thiol cascade chemistry with convergent evolution. J. Mol. Biol. 362 (2006) 1–17. [PMID: 16905151]

[EC 1.20.4.1 created 2000 as EC 1.97.1.5, transferred 2001 to EC 1.20.4.1, modified 2015, modified 2019, modified 2020]

*EC

1.20.4.4

Accepted name:

arsenate reductase (thioredoxin)

Reaction:

arsenate + thioredoxin = arsenite + thioredoxin disulfide + H₂O

For diagram of arsenate catabolism, click here

Other name(s):

ArsC (ambiguous)

Systematic name:

arsenate:thioredoxin oxidoreductase

Comments:

The enzyme, characterized in bacteria of the Firmicutes phylum, is specific for thioredoxin [1]. It has no activity with glutaredoxin [cf. EC 1.20.4.1, arsenate reductase (glutaredoxin)]. Although the arsenite formed is more toxic than arsenate, it can be extruded from some bacteria by EC 7.3.2.7, arsenite-transporting ATPase; in other organisms, arsenite can be methylated by EC 2.1.1.137, arsenite methyltransferase, in a pathway that produces non-toxic organoarsenical compounds. The enzyme also has the activity of EC 3.1.3.48, protein-tyrosine-phosphatase [3].

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB

References:

1.	Ji, G., Garber, E.A., Armes, L.G., Chen, C.M., Fuchs, J.A. and Silver, S. Arsenate reductase of Staphylococcus aureus plasmid pI258. Biochemistry 33 (1994) 7294–7299. [PMID: 8003493]
2.	Messens, J., Hayburn, G., Desmyter, A., Laus, G. and Wyns, L. The essential catalytic redox couple in arsenate reductase from Staphylococcus aureus. Biochemistry 38 (1999) 16857–16865. [DOI] [PMID: 10606519]
3.	Zegers, I., Martins, J.C., Willem, R., Wyns, L. and Messens, J. Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty. Nat. Struct. Biol. 8 (2001) 843–847. [DOI] [PMID: 11573087]
4.	Messens, J., Martins, J.C., Van Belle, K., Brosens, E., Desmyter, A., De Gieter, M., Wieruszeski, J.M., Willem, R., Wyns, L. and Zegers, I. All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade. Proc. Natl. Acad. Sci. USA 99 (2002) 8506–8511. [DOI] [PMID: 12072565]

[EC 1.20.4.4 created 2015, modified 2019]

2.1.1.353

Accepted name:

demethylluteothin O-methyltransferase

Reaction:

S-adenosyl-L-methionine + demethylluteothin = S-adenosyl-L-homocysteine + luteothin

For diagram of aureothin catabolism, click here

Glossary:

Other name(s):

aurI (gene name)

Systematic name:

S-adenosyl-L-methionine:demethylluteothin O-methyltransferase

Comments:

The enzyme, characterized from the bacterium Streptomyces thioluteus, participates in the biosynthesis of the antibiotic aureothin. An orthologous enzyme in the bacteria Streptomyces orinoci and Streptomyces spectabilis catalyses a similar reaction in the biosynthesis of spectinabilin.

Links to other databases:

References:

1.	He, J., Muller, M. and Hertweck, C. Formation of the aureothin tetrahydrofuran ring by a bifunctional cytochrome P450 monooxygenase. J. Am. Chem. Soc. 126 (2004) 16742–16743. [PMID: 15612710]
2.	Muller, M., He, J. and Hertweck, C. Dissection of the late steps in aureothin biosynthesis. ChemBioChem 7 (2006) 37–39. [PMID: 16292785]

[EC 2.1.1.353 created 2019]

*EC

2.3.1.9

Accepted name:

acetyl-CoA C-acetyltransferase

Reaction:

2 acetyl-CoA = CoA + acetoacetyl-CoA (overall reaction)
(1a) acetyl-CoA + [acetyl-CoA C-acetyltransferase]-L-cysteine = [acetyl-CoA C-acetyltransferase]-S-acetyl-L-cysteine + CoA
(1b) [acetyl-CoA C-acetyltransferase]-S-acetyl-L-cysteine + acetyl-CoA = acetoacetyl-CoA + [acetyl-CoA C-acetyltransferase]-L-cysteine

For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here and for diagram of mevalonate biosynthesis, click here

Other name(s):

acetoacetyl-CoA thiolase; β-acetoacetyl coenzyme A thiolase; 2-methylacetoacetyl-CoA thiolase [misleading]; 3-oxothiolase; acetyl coenzyme A thiolase; acetyl-CoA acetyltransferase; acetyl-CoA:N-acetyltransferase; thiolase II; type II thiolase

Systematic name:

acetyl-CoA:acetyl-CoA C-acetyltransferase

Comments:

The enzyme, found in both eukaryotes and prokaryotes, catalyses the Claisen condensation of an acetyl-CoA and an acyl-CoA (often another acetyl-CoA), leading to the formation of an acyl-CoA that is longer by two carbon atoms. The reaction starts with the acylation of a nucleophilic cysteine at the active site, usually by acetyl-CoA but potentially by a different acyl-CoA, with concomitant release of CoA. In the second step the acyl group is transferred to an acetyl-CoA molecule. cf. EC 2.3.1.16, acetyl-CoA C-acyltransferase.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9027-46-7

References:

1.	Lynen, F. and Ochoa, S. Enzymes of fatty acid metabolism. Biochim. Biophys. Acta 12 (1953) 299–314. [DOI] [PMID: 13115439]
2.	Stern, J.R., Drummond, G.I., Coon, M.J. and del Campillo, A. Enzymes of ketone body metabolism. I. Purification of an acetoacetate-synthesizing enzyme from ox liver. J. Biol. Chem. 235 (1960) 313–317. [PMID: 13834445]

[EC 2.3.1.9 created 1961, modified 2019]

*EC

2.3.1.16

Accepted name:

acetyl-CoA C-acyltransferase

Reaction:

acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA (overall reaction)
(1a) [acetyl-CoA C-acyltransferase]-S-acyl-L-cysteine + acetyl-CoA = 3-oxoacyl-CoA + [acetyl-CoA C-acyltransferase]-L-cysteine
(1b) acyl-CoA + [acetyl-CoA C-acyltransferase]-L-cysteine = [acetyl-CoA C-acyltransferase]-S-acyl-L-cysteine + CoA

For diagram of aerobic phenylacetate catabolism, click here and for diagram of Benzoyl-CoA catabolism, click here

Other name(s):

β-ketothiolase; 3-ketoacyl-CoA thiolase; KAT; β-ketoacyl coenzyme A thiolase; β-ketoacyl-CoA thiolase; β-ketoadipyl coenzyme A thiolase; β-ketoadipyl-CoA thiolase; 3-ketoacyl CoA thiolase; 3-ketoacyl coenzyme A thiolase; 3-ketoacyl thiolase; 3-ketothiolase; 3-oxoacyl-CoA thiolase; 3-oxoacyl-coenzyme A thiolase; 6-oxoacyl-CoA thiolase; acetoacetyl-CoA β-ketothiolase; acetyl-CoA acyltransferase; ketoacyl-CoA acyltransferase; ketoacyl-coenzyme A thiolase; long-chain 3-oxoacyl-CoA thiolase; oxoacyl-coenzyme A thiolase; pro-3-ketoacyl-CoA thiolase; thiolase I; type I thiolase; 2-methylacetoacetyl-CoA thiolase [misleading]

Systematic name:

acyl-CoA:acetyl-CoA C-acyltransferase

Comments:

The enzyme, found in both eukaryotes and in prokaryotes, is involved in degradation pathways such as fatty acid β-oxidation. The enzyme acts on 3-oxoacyl-CoAs to produce acetyl-CoA and an acyl-CoA shortened by two carbon atoms. The reaction starts with the acylation of a nucleophilic cysteine at the active site by a 3-oxoacyl-CoA, with the concomitant release of acetyl-CoA. In the second step the acyl group is transferred to CoA. Most enzymes have a broad substrate range for the 3-oxoacyl-CoA. cf. EC 2.3.1.9, acetyl-CoA C-acetyltransferase.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 9029-97-4

References:

1.	Beinert, H., Bock, R.M., Goldman, D.S., Green, D.E., Mahler, H.R., Mii, S., Stansly, P.G. and Wakil, S.J. A synthesis of dl-cortisone acetate. J. Am. Chem. Soc. 75 (1953) 4111–4112.
2.	Goldman, D.S. Studies on the fatty acid oxidizing system of animal tissue. VII. The β-ketoacyl coenzyme A cleavage enzyme. J. Biol. Chem. 208 (1954) 345–357. [PMID: 13174544]
3.	Stern, J.R., Coon, M.J. and del Campillo, A. Enzymatic breakdown and synthesis of acetoacetate. Nature 171 (1953) 28–30. [PMID: 13025466]

[EC 2.3.1.16 created 1961, modified 2019]

*EC

2.3.1.85

Accepted name:

fatty-acid synthase system

Reaction:

acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H⁺ = a long-chain fatty acid + (n+1) CoA + n CO₂ + 2n NADP⁺

Glossary:

a long-chain-fatty acid = a fatty acid with an aliphatic chain of 13–22 carbons.

Other name(s):

FASN (gene name); fatty-acid synthase

Systematic name:

acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester-hydrolysing)

Comments:

The animal enzyme is a multi-functional protein catalysing the reactions of EC 2.3.1.38 [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase, EC 2.3.1.41 β-ketoacyl-[acyl-carrier-protein] synthase I, EC 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase, EC 4.2.1.59 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.39 enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 3.1.2.14 oleoyl-[acyl-carrier-protein] hydrolase. cf. EC 2.3.1.86, fatty-acyl-CoA synthase system.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9045-77-6

References:

1.	Stoops, J.K., Ross, P., Arslanian, M.J., Aune, K.C., Wakil, S.J. and Oliver, R.M. Physicochemical studies of the rat liver and adipose fatty acid synthetases. J. Biol. Chem. 254 (1979) 7418–7426. [PMID: 457689]
2.	Wakil, S.J., Stoops, J.K. and Joshi, V.C. Fatty acid synthesis and its regulation. Annu. Rev. Biochem. 52 (1983) 537–579. [DOI] [PMID: 6137188]

[EC 2.3.1.85 created 1984, modified 2019]

*EC

2.3.1.86

Accepted name:

fatty-acyl-CoA synthase system

Reaction:

acetyl-CoA + n malonyl-CoA + 2n NADPH + 4n H⁺ = long-chain-acyl-CoA + n CoA + n CO₂ + 2n NADP⁺

Other name(s):

yeast fatty acid synthase; FAS1 (gene name); FAS2 (gene name); fatty-acyl-CoA synthase

Systematic name:

acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing)

Comments:

The enzyme from yeasts (Ascomycota and Basidiomycota) is a multi-functional protein complex composed of two subunits. One subunit catalyses the reactions EC 1.1.1.100, 3-oxoacyl-[acyl-carrier-protein] reductase and EC 2.3.1.41, β-ketoacyl-[acyl-carrier-protein] synthase I, while the other subunit catalyses the reactions of EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, EC 2.3.1.39, [acyl-carrier-protein] S-malonyltransferase, EC 4.2.1.59, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 1.3.1.10, enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific) and EC 1.1.1.279, (R)-3-hydroxyacid-ester dehydrogenase. The enzyme system differs from the animal system (EC 2.3.1.85, fatty-acid synthase system) in that the enoyl reductase domain requires FMN as a cofactor, and the ultimate product is an acyl-CoA (usually palmitoyl-CoA) instead of a free fatty acid.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 94219-29-1

References:

1.	Schweitzer, E., Kniep, B., Castorph, H. and Holzner, U. Pantetheine-free mutants of the yeast fatty-acid-synthetase complex. Eur. J. Biochem. 39 (1973) 353–362. [DOI] [PMID: 4590449]
2.	Wakil, S.J., Stoops, J.K. and Joshi, V.C. Fatty acid synthesis and its regulation. Annu. Rev. Biochem. 52 (1983) 537–579. [DOI] [PMID: 6137188]
3.	Tehlivets, O., Scheuringer, K. and Kohlwein, S.D. Fatty acid synthesis and elongation in yeast. Biochim. Biophys. Acta 1771 (2007) 255–270. [DOI] [PMID: 16950653]

[EC 2.3.1.86 created 1984, modified 2003, modified 2013, modified 2019]

*EC

2.3.1.161

Accepted name:

lovastatin nonaketide synthase

Reaction:

9 malonyl-CoA + 11 NADPH + 10 H⁺ + S-adenosyl-L-methionine + holo-[lovastatin nonaketide synthase] = dihydromonacolin L-[lovastatin nonaketide synthase] + 9 CoA + 9 CO₂ + 11 NADP⁺ + S-adenosyl-L-homocysteine + 6 H₂O

For diagram of polyketides biosynthesis, click here

Glossary:

dihydromonacolin L acid = (3R,5R)-7-[(1S,2S,4aR,6R,8aS)-2,6-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate

Other name(s):

LNKS; LovB; LovC; acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing, thioester-hydrolysing)

Systematic name:

acyl-CoA:malonyl-CoA C-acyltransferase (dihydromonacolin L acid-forming)

Comments:

This fungal enzyme system comprises a multi-functional polyketide synthase (PKS) and an enoyl reductase. The PKS catalyses many of the chain building reactions of EC 2.3.1.85, fatty-acid synthase system, as well as a reductive methylation and a Diels-Alder reaction, while the reductase is responsible for three enoyl reductions that are necessary for dihydromonacolin L acid production.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 235426-97-8

References:

1.	Ma, S.M., Li, J.W., Choi, J.W., Zhou, H., Lee, K.K., Moorthie, V.A., Xie, X., Kealey, J.T., Da Silva, N.A., Vederas, J.C. and Tang, Y. Complete reconstitution of a highly reducing iterative polyketide synthase. Science 326 (2009) 589–592. [DOI] [PMID: 19900898]
2.	Kennedy, J., Auclair, K., Kendrew, S.G., Park, C., Vederas, J.C. and Hutchinson, C.R. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284 (1999) 1368–1372. [DOI] [PMID: 10334994]
3.	Auclair, K., Sutherland, A., Kennedy, J., Witter, D.J., van der Heever, J.P., Hutchinson, C.R. and Vederas, J.C. Lovastatin nonaketide synthase catalyses an intramolecular Diels-Alder reaction of a substrate analogue. J. Am. Chem. Soc. 122 (2000) 11519–11520.

[EC 2.3.1.161 created 2002, modified 2015, modified 2016, modified 2019]

2.3.1.281

Accepted name:

5-hydroxydodecatetraenal polyketide synthase

Reaction:

6 malonyl-CoA + 5 NADPH + NADH + 6 H⁺ = (2E,5S,6E,8E,10E)-5-hydroxydodeca-2,6,8,10-tetraenal + 6 CoA + 5 NADP⁺ + NAD⁺ + 6 CO₂ + 4 H₂O

For diagram of polyketides biosynthesis, click here

Glossary:

coelimycin P1 = N-[(3R)-8-[(2E)-but-2-enoyl]-6-[(2E)-5,6-dihydropyridin-2(1H)-ylidene]-2-oxo-3,4-dihydro-2H,6H-1,5-oxathiocin-3-yl]acetamide

Other name(s):

cpkABC (gene names)

Systematic name:

malonyl-CoA:malonyl-CoA malonyltransferase ((2E,5S,6E,8E,10E)-5-hydroxydodeca-2,6,8,10-tetraenal-forming)

Comments:

This polyketide synthase enzyme, characterized from the bacterium Streptomyces coelicolor A3(2), catalyses the first reaction in the biosynthesis of coelimycin P1. The enzyme is made of three proteins which together comprise six modules that contain a total of 28 domains. An NADH-dependent terminal reductase domain at the C-terminus of the enzyme catalyses the reductive release of the product.

Links to other databases:

References:

1.	Pawlik, K., Kotowska, M., Chater, K.F., Kuczek, K. and Takano, E. A cryptic type I polyketide synthase (cpk) gene cluster in Streptomyces coelicolor A3(2). Arch. Microbiol. 187 (2007) 87–99. [PMID: 17009021]
2.	Awodi, U.R., Ronan, J.L., Masschelein, J., Santos, E.LC. and Challis, G.L. Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis. Chem. Sci. 8 (2017) 411–415. [PMID: 28451186]

[EC 2.3.1.281 created 2019]

2.3.1.282

Accepted name:

phenolphthiocerol/phthiocerol/phthiodiolone dimycocerosyl transferase

Reaction:

(1) 2 a mycocerosyl-[mycocerosic acid synthase] + a phthiocerol = a dimycocerosyl phthiocerol + 2 holo-[mycocerosic acid synthase]
(2) 2 a mycocerosyl-[mycocerosic acid synthase] + a phthiodiolone = a dimycocerosyl phthiodiolone + 2 holo-[mycocerosic acid synthase]
(3) 2 a mycocerosyl-[mycocerosic acid synthase] + a phenolphthiocerol = a dimycocerosyl phenolphthiocerol + 2 holo-[mycocerosic acid synthase]

Glossary:

a mycocerosate = 2,4,6-trimethyl- and 2,4,6,8-tetramethyl-2-alkanoic acids present in many pathogenic mycobacteria. The chiral centers bearing the methyl groups have an L (levorotatory) stereo configuration.
a phthiocerol = a linear carbohydrate molecule to which one methoxyl group, one methyl group, and two secondary hydroxyl groups are attached.
a phthiodiolone = an intermediate in phthiocerol biosynthesis, containing an oxo group where phthiocerols contain a methoxyl group
a phenolphthiocerol = a compound related to phthiocerol that contains a phenol group at the ω end of the molecule

Other name(s):

papA5 (gene name)

Systematic name:

mycocerosyl-[mycocerosic acid synthase]:phenolphthiocerol/phthiocerol/phthiodiolone dimycocerosyl transferase

Comments:

The enzyme, present in certain pathogenic species of mycobacteria, catalyses the transfer of mycocerosic acids to the two hydroxyl groups at the common lipid core of phthiocerol, phthiodiolone, and phenolphthiocerol, forming dimycocerosate esters. The fatty acid precursors of mycocerosic acids are activated by EC 6.2.1.49, long-chain fatty acid adenylyltransferase FadD28, which loads them onto EC 2.3.1.111, mycocerosate synthase. That enzyme extends the precursors to form mycocerosic acids that remain attached until transferred by EC 2.3.1.282.

Links to other databases:

References:

1.	Onwueme, K.C., Ferreras, J.A., Buglino, J., Lima, C.D. and Quadri, L.E. Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5. Proc. Natl. Acad. Sci. USA 101 (2004) 4608–4613. [PMID: 15070765]
2.	Buglino, J., Onwueme, K.C., Ferreras, J.A., Quadri, L.E. and Lima, C.D. Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis. J. Biol. Chem. 279 (2004) 30634–30642. [PMID: 15123643]
3.	Chavadi, S.S., Onwueme, K.C., Edupuganti, U.R., Jerome, J., Chatterjee, D., Soll, C.E. and Quadri, L.E. The mycobacterial acyltransferase PapA5 is required for biosynthesis of cell wall-associated phenolic glycolipids. Microbiology 158 (2012) 1379–1387. [PMID: 22361940]
4.	Touchette, M.H., Bommineni, G.R., Delle Bovi, R.J., Gadbery, J.E., Nicora, C.D., Shukla, A.K., Kyle, J.E., Metz, T.O., Martin, D.W., Sampson, N.S., Miller, W.T., Tonge, P.J. and Seeliger, J.C. Diacyltransferase activity and chain length specificity of Mycobacterium tuberculosis PapA5 in the synthesis of alkyl β-diol lipids. Biochemistry 54 (2015) 5457–5468. [DOI] [PMID: 26271001]

[EC 2.3.1.282 created 2019]

2.3.1.283

Accepted name:

2′-acyl-2-O-sulfo-trehalose (hydroxy)phthioceranyltransferase

Reaction:

a (hydroxy)phthioceranyl-[(hydroxy)phthioceranic acid synthase] + 2′-palmitoyl/stearoyl-2-O-sulfo-α,α-trehalose = a 3′-(hydroxy)phthioceranyl-2′-palmitoyl/stearoyl-2-O-sulfo-α,α-trehalose + holo-[(hydroxy)phthioceranic acid synthase]

Other name(s):

papA1 (gene name)

Systematic name:

(hydroxy)phthioceranyl-[(hydroxy)phthioceranic acid synthase]:2′-acyl-2-O-sulfo-α,α-trehalose 3′-(hydroxy)phthioceranyltransferase

Comments:

This mycobacterial enzyme catalyses the acylation of 2′-palmitoyl/stearoyl-2-O-sulfo-α,α-trehalose at the 3′ position by a (hydroxy)phthioceranoyl group during the biosynthesis of mycobacterial sulfolipids.

Links to other databases:

References:

1.	Bhatt, K., Gurcha, S.S., Bhatt, A., Besra, G.S. and Jacobs, W.R., Jr. Two polyketide-synthase-associated acyltransferases are required for sulfolipid biosynthesis in Mycobacterium tuberculosis. Microbiology 153 (2007) 513–520. [PMID: 17259623]
2.	Kumar, P., Schelle, M.W., Jain, M., Lin, F.L., Petzold, C.J., Leavell, M.D., Leary, J.A., Cox, J.S. and Bertozzi, C.R. PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. Proc. Natl. Acad. Sci. USA 104 (2007) 11221–11226. [PMID: 17592143]

[EC 2.3.1.283 created 2019]

2.3.1.284

Accepted name:

3′-(hydroxy)phthioceranyl-2′-palmitoyl(stearoyl)-2-O-sulfo-trehalose (hydroxy)phthioceranyltransferase

Reaction:

3 3′-(hydroxy)phthioceranyl-2′-palmitoyl(stearoyl)-2-O-sulfo-α,α-trehalose = 3,6,6′-tris-(hydroxy)phthioceranyl-2-palmitoyl(stearoyl)-2′-sulfo-α-alpha-trehalose + 2 2′-palmitoyl/stearoyl-2-O-sulfo-α,α-trehalose

Glossary:

3,6,6′-tris-(hydroxy)phthioceranyl-2-palmitoyl(stearoyl)-2′-sulfo-α-alpha-trehalose = a mycobacterial sulfolipid

Other name(s):

chp1 (gene name)

Systematic name:

3′-(hydroxy)phthioceranyl-2′-palmitoyl(stearoyl)-2-O-sulfo-α,α-trehalose:3′-(hydroxy)phthioceranyl-2′-palmitoyl(stearoyl)-2-O-sulfo-α,α-trehalose 6,6′-di(hydroxy)phthioceranyltransferase

Comments:

The enzyme, present in mycobacteria, catalyses the ultimate step in the biosynthesis of mycobacterial sulfolipids. It catalyses two successive transfers of a (hydroxy)phthioceranyl group from two diacylated intermediates to third diacylated intermediate, generating the tetraacylated sulfolipid.

Links to other databases:

References:

Seeliger, J.C., Holsclaw, C.M., Schelle, M.W., Botyanszki, Z., Gilmore, S.A., Tully, S.E., Niederweis, M., Cravatt, B.F., Leary, J.A. and Bertozzi, C.R. Elucidation and chemical modulation of sulfolipid-1 biosynthesis in Mycobacterium tuberculosis. J. Biol. Chem. 287 (2012) 7990–8000. [PMID: 22194604]

[EC 2.3.1.284 created 2019]

2.3.1.285

Accepted name:

(13S,14R)-1,13-dihydroxy-N-methylcanadine 13-O-acetyltransferase

Reaction:

acetyl-CoA + (13S,14R)-1,13-dihydroxy-cis-N-methylcanadine = (13S,14R)-13-O-acetyl-1-hydroxy-cis-N-methylcanadine + CoA

For diagram of noscapine biosynthesis, click here

Other name(s):

AT1 (gene name)

Systematic name:

acetyl-CoA:(13S,14R)-1,13-dihydroxy-cis-N-methylcanadine O-acetyltransferase

Comments:

The enzyme, characterized from the plant Papaver somniferum (opium poppy), participates in the biosynthesis of the isoquinoline alkaloid noscapine.

Links to other databases:

References:

1.	Dang, T.T., Chen, X. and Facchini, P.J. Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nat. Chem. Biol. 11 (2015) 104–106. [DOI] [PMID: 25485687]
2.	Li, Y., Li, S., Thodey, K., Trenchard, I., Cravens, A. and Smolke, C.D. Complete biosynthesis of noscapine and halogenated alkaloids in yeast. Proc. Natl. Acad. Sci. USA 115 (2018) E3922–E3931. [DOI] [PMID: 29610307]

[EC 2.3.1.285 created 2019]

2.3.1.286

Accepted name:

protein acetyllysine N-acetyltransferase

Reaction:

[protein]-N⁶-acetyl-L-lysine + NAD⁺ + H₂O = [protein]-L-lysine + 2′′-O-acetyl-ADP-D-ribose + nicotinamide (overall reaction)
(1a) [protein]-N⁶-acetyl-L-lysine + NAD⁺ = [protein]-N⁶-[1,1-(5-adenosylyl-α-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + nicotinamide
(1b) [protein]-N⁶-[1,1-(5-adenosylyl-α-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + H₂O = [protein]-L-lysine + 2′′-O-acetyl-ADP-D-ribose

Other name(s):

Sir2; protein lysine deacetylase; NAD⁺-dependent protein deacetylase

Systematic name:

[protein]-N⁶-acetyl-L-lysine:NAD⁺ N-acetyltransferase (NAD⁺-hydrolysing; 2′′-O-acetyl-ADP-D-ribose-forming)

Comments:

The enzyme, found in all domains of life, is involved in gene regulation by deacetylating proteins. Some of the 2′′-O-acetyl-ADP-D-ribose converts non-enzymically to 3′′-O-acetyl-ADP-D-ribose.

Links to other databases:

References:

1.	Landry, J., Slama, J.T. and Sternglanz, R. Role of NAD⁺ in the deacetylase activity of the SIR2-like proteins. Biochem. Biophys. Res. Commun. 278 (2000) 685–690. [PMID: 11095969]
2.	Sauve, A.A., Celic, I., Avalos, J., Deng, H., Boeke, J.D. and Schramm, V.L. Chemistry of gene silencing: the mechanism of NAD⁺-dependent deacetylation reactions. Biochemistry 40 (2001) 15456–15463. [PMID: 11747420]
3.	Min, J., Landry, J., Sternglanz, R. and Xu, R.M. Crystal structure of a SIR2 homolog-NAD complex. Cell 105 (2001) 269–279. [PMID: 11336676]
4.	Jackson, M.D., Schmidt, M.T., Oppenheimer, N.J. and Denu, J.M. Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases. J. Biol. Chem. 278 (2003) 50985–50998. [PMID: 14522996]
5.	Sauve, A.A., Wolberger, C., Schramm, V.L. and Boeke, J.D. The biochemistry of sirtuins. Annu. Rev. Biochem. 75 (2006) 435–465. [PMID: 16756498]

[EC 2.3.1.286 created 2019]

2.3.1.287

Accepted name:

phthioceranic/hydroxyphthioceranic acid synthase

Reaction:

(1) 8 (S)-methylmalonyl-CoA + palmitoyl-[(hydroxy)phthioceranic acid synthase] + 16 NADPH + 16 H⁺ = 8 CoA + C₄₀-phthioceranyl-[(hydroxy)phthioceranic acid synthase] + 16 NADP⁺ + 8 CO₂ + 8 H₂O
(2) 7 (S)-methylmalonyl-CoA + palmitoyl-[(hydroxy)phthioceranic acid synthase] + 14 NADPH + 14 H⁺ = 7 CO₂ + C₃₇-phthioceranyl-[(hydroxy)phthioceranic acid synthase] + 14 NADP⁺ + 7 CoA + 7 H₂O

Other name(s):

msl2 (gene name); PKS2

Systematic name:

(S)-methylmalonyl-CoA:palmitoyl-[(hydroxy)phthioceranic acid synthase] methylmalonyltransferase (phthioceranyl-[(hydroxy)phthioceranic acid synthase]-forming)

Comments:

This mycobacterial polyketide enzyme produces the hepta- and octa-methylated fatty acids known as phthioceranic acids, and presumably their hydroxylated versions. Formation of hepta- and octamethylated products depends on whether the enzyme incorporates seven or eight methylmalonyl-CoA extender units, respectively. Formation of hydroxylated products may result from the enzyme skipping the dehydratase (DH) and enoylreductase (ER) domains during the first cycle of condensation [2].

Links to other databases:

References:

1.	Sirakova, T.D., Thirumala, A.K., Dubey, V.S., Sprecher, H. and Kolattukudy, P.E. The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J. Biol. Chem. 276 (2001) 16833–16839. [DOI] [PMID: 11278910]
2.	Gokhale, R.S., Saxena, P., Chopra, T. and Mohanty, D. Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. Nat. Prod. Rep. 24 (2007) 267–277. [PMID: 17389997]
3.	Passemar, C., Arbues, A., Malaga, W., Mercier, I., Moreau, F., Lepourry, L., Neyrolles, O., Guilhot, C. and Astarie-Dequeker, C. Multiple deletions in the polyketide synthase gene repertoire of Mycobacterium tuberculosis reveal functional overlap of cell envelope lipids in host-pathogen interactions. Cell Microbiol 16 (2014) 195–213. [PMID: 24028583]

[EC 2.3.1.287 created 2019]

2.4.1.361

Accepted name:

GDP-mannose:di-myo-inositol-1,3′-phosphate β-1,2-mannosyltransferase

Reaction:

2 GDP-α-D-mannose + bis(myo-inositol) 1,3′-phosphate = 2 GDP + 2-O-(β-D-mannosyl-(1→2)-β-D-mannosyl)-bis(myo-inositol) 1,3′-phosphate (overall reaction)
(1a) GDP-α-D-mannose + bis(myo-inositol) 1,3′-phosphate = GDP + 2-O-(β-D-mannosyl)-bis(myo-inositol) 1,3′-phosphate
(1b) GDP-α-D-mannose + 2-O-(β-D-mannosyl)-bis(myo-inositol) 1,3′-phosphate = GDP + 2-O-(β-D-mannosyl-(1→2)-β-D-mannosyl)-bis(myo-inositol) 1,3′-phosphate

Other name(s):

MDIP synthase

Systematic name:

GDP-α-D-mannose:bis(myo-inositol)-1,3′-phosphate 2-β-D-mannosyltransferase

Comments:

The enzyme from the hyperthermophilic bacterium Thermotoga maritima is involved in the synthesis of the solutes 2-O-(β-D-mannosyl)-bis(myo-inositol) 1,3′-phosphate and 2-O-(β-D-mannosyl-(1→2)-β-D-mannosyl)-bis(myo-inositol) 1,3′-phosphate.

Links to other databases:

References:

1.	Rodrigues, M.V., Borges, N., Almeida, C.P., Lamosa, P. and Santos, H. A unique β-1,2-mannosyltransferase of Thermotoga maritima that uses di-myo-inositol phosphate as the mannosyl acceptor. J. Bacteriol. 191 (2009) 6105–6115. [PMID: 19648237]

[EC 2.4.1.361 created 2019]

2.4.1.362

Accepted name:

α-(1→3) branching sucrase

Reaction:

sucrose + a (1→6)-α-D-glucan = D-fructose + a (1→6)-α-D-glucan containing a (1→3)-α-D-glucose branch

Other name(s):

branching sucrase A; BRS-A; brsA (gene name)

Systematic name:

sucrose:(1→6)-α-D-glucan 3-α-D-[(1→3)-α-D-glucosyl]-transferase

Comments:

The enzyme from Leuconostoc spp. is responsible for producing α-(1→3) branches in α-(1→6) glucans by transferring the glucose residue from fructose to a 3-hydroxyl group of a glucan.

Links to other databases:

References:

1.	Vuillemin, M., Claverie, M., Brison, Y., Severac, E., Bondy, P., Morel, S., Monsan, P., Moulis, C. and Remaud-Simeon, M. Characterization of the first α-(1→3) branching sucrases of the GH70 family. J. Biol. Chem. 291 (2016) 7687–7702. [PMID: 26763236]
2.	Moulis, C., Andre, I. and Remaud-Simeon, M. GH13 amylosucrases and GH70 branching sucrases, atypical enzymes in their respective families. Cell. Mol. Life Sci. 73 (2016) 2661–2679. [PMID: 27141938]

[EC 2.4.1.362 created 2019]

2.4.1.363

Accepted name:

ginsenoside 20-O-glucosyltransferase

Reaction:

UDP-α-D-glucose + (20S)-protopanaxadiol = UDP + ginsenoside C-K

For diagram of protopanaxadiol glucoside biosynthesis, click here

Glossary:

(20S)-protopanaxadiol = (3β,12β)-dammar-24-ene-3,12,20-triol
ginsenoside C-K = (3β,12β)-3,12-dihydroxydammar-24-en-20-yl β-D-glucopyranoside

Other name(s):

UGT71A27 (gene name)

Systematic name:

UDP-α-D-glucose:(20S)-protopanaxadiol 20-O-glucosyltransferase (configuration-inverting)

Comments:

The enzyme, characterized from the plant Panax ginseng, transfers a glucosyl moiety to the free C20(S)-OH group of dammarane derivative substrates, including protopanaxatriol, dammarenediol II, (20S)-ginsenoside Rh2, and (20S)-ginsenoside Rg3. It does not act on the 20R epimer of protopanaxadiol, or on ginsenosides that are glucosylated at the C-6 position, such as ginsenoside Rh1 or ginsenoside Rg2.

Links to other databases:

References:

1.	Yan, X., Fan, Y., Wei, W., Wang, P., Liu, Q., Wei, Y., Zhang, L., Zhao, G., Yue, J. and Zhou, Z. Production of bioactive ginsenoside compound K in metabolically engineered yeast. Cell Res. 24 (2014) 770–773. [PMID: 24603359]
2.	Wei, W., Wang, P., Wei, Y., Liu, Q., Yang, C., Zhao, G., Yue, J., Yan, X. and Zhou, Z. Characterization of Panax ginseng UDP-glycosyltransferases catalyzing protopanaxatriol and biosyntheses of bioactive ginsenosides F1 and Rh1 in metabolically engineered yeasts. Mol. Plant 8 (2015) 1412–1424. [PMID: 26032089]

[EC 2.4.1.363 created 2019]

2.4.1.364

Accepted name:

protopanaxadiol-type ginsenoside 3-O-glucosyltransferase

Reaction:

(1) UDP-α-D-glucose + (20S)-protopanaxadiol = UDP + (20S)-ginsenoside Rh2
(2) UDP-α-D-glucose + ginsenoside C-K = UDP + ginsenoside F2

For diagram of protopanaxadiol glucoside biosynthesis, click here

Glossary:

(20S)-protopanaxadiol = (3β,12β)-dammar-24-ene-3,12,20-triol
ginsenoside C-K = (3β,12β)-3,12-dihydroxydammar-24-en-20-yl β-D-glucopyranoside

Other name(s):

UGT74AE2 (gene name)

Systematic name:

UDP-α-D-glucose:protopanaxadiol-type ginsenoside 3-O-glucosyltransferase (configuration-retaining)

Comments:

The enzyme, characterized from the plant Panax ginseng, transfers a glucosyl moiety to the free C-3-OH group of (20S)-protopanaxadiol and ginsenoside C-K.

Links to other databases:

References:

1.	Jung, S.C., Kim, W., Park, S.C., Jeong, J., Park, M.K., Lim, S., Lee, Y., Im, W.T., Lee, J.H., Choi, G. and Kim, S.C. Two ginseng UDP-glycosyltransferases synthesize ginsenoside Rg3 and Rd. Plant Cell Physiol. 55 (2014) 2177–2188. [PMID: 25320211]

[EC 2.4.1.364 created 2019]

2.4.1.365

Accepted name:

protopanaxadiol-type ginsenoside-3-O-glucoside 2′′-O-glucosyltransferase

Reaction:

(1) UDP-α-D-glucose + (20S)-ginsenoside Rh2 = UDP + (20S)-ginsenoside Rg3
(2) UDP-α-D-glucose + ginsenoside F2 = UDP + ginsenoside Rd

For diagram of protopanaxadiol glucoside biosynthesis, click here

Glossary:

(20S)-ginsenoside Rh2 = (3β,12β)-12,20-dihydroxydammar-24-en-3-yl β-D-glucopyranoside
ginsenoside F2 = (3β,12β)-20-(β-D-glucopyranosyloxy)-12-hydroxydammar-24-en-3-yl β-D-glucopyranoside

Other name(s):

UGT94Q2 (gene name)

Systematic name:

UDP-α-D-glucose:3-O-glucosyl-protopanaxadiol-type ginsenoside 2′′-O-glucosyltransferase

Comments:

The enzyme, characterized from the plant Panax ginseng, transfers a glucosyl moiety to the 2′′ position of the glucose moiety in the protopanaxadiol-type ginsenoside-3-O-glucosides (20S)-ginsenoside Rh2 and ginsenoside F2.

Links to other databases:

References:

1.	Jung, S.C., Kim, W., Park, S.C., Jeong, J., Park, M.K., Lim, S., Lee, Y., Im, W.T., Lee, J.H., Choi, G. and Kim, S.C. Two ginseng UDP-glycosyltransferases synthesize ginsenoside Rg3 and Rd. Plant Cell Physiol. 55 (2014) 2177–2188. [PMID: 25320211]

[EC 2.4.1.365 created 2019]

2.4.1.366

Accepted name:

ginsenoside F1 6-O-glucosyltransferase

Reaction:

UDP-α-D-glucose + ginsenoside F1 = UDP + (20S)-ginsenoside Rg1

For diagram of protopanaxatriol glucoside biosynthesis, click here

Glossary:

ginsenoside F1 = 3β,6α,12β-trihydroxydammar-24-en-20-yl β-D-glucopyranoside

Other name(s):

UGTPg101 (gene name)

Systematic name:

UDP-α-D-glucose:ginsenoside F1 6-O-glucosyltransferase

Comments:

The enzyme, characterized from the plant Panax ginseng, glucosylates the C-6 position of ginsenoside F1. The enzyme also glucosylates the C-20 position of protopanaxatriol, which forms ginsenoside F1 (cf. EC 2.4.1.363, ginsenoside 20-O-glucosyltransferase). However, unlike EC 2.4.1.367, ginsenoside 6-O-glucosyltransferase, it is not able to glucosylate the C-6 position of protopanaxatriol when position C-20 is not glucosylated.

Links to other databases:

References:

Wei, W., Wang, P., Wei, Y., Liu, Q., Yang, C., Zhao, G., Yue, J., Yan, X. and Zhou, Z. Characterization of Panax ginseng UDP-glycosyltransferases catalyzing protopanaxatriol and biosyntheses of bioactive ginsenosides F1 and Rh1 in metabolically engineered yeasts. Mol. Plant 8 (2015) 1412–1424. [PMID: 26032089]

[EC 2.4.1.366 created 2019]

2.4.1.367

Accepted name:

ginsenoside 6-O-glucosyltransferase

Reaction:

(1) UDP-α-D-glucose + protopanaxatriol = UDP + ginsenoside Rh1
(2) UDP-α-D-glucose + ginsenoside F1 = UDP + (20S)-ginsenoside Rg1

For diagram of protopanaxatriol glucoside biosynthesis, click here

Glossary:

protopanaxatriol = (3β,6α,12β)-dammar-24-ene-3,6,12,20-tetrol
ginsenoside F1 = (3β,6α,12β)-trihydroxydammar-24-en-20-yl β-D-glucopyranoside

Other name(s):

UGTPg100 (gene name)

Systematic name:

UDP-α-D-glucose:ginsenoside 6-O-glucosyltransferase

Comments:

The enzyme, characterized from the plant Panax ginseng, glucosylates the C-6 position of protopanaxatriol and ginsenoside F1.

Links to other databases:

References:

[EC 2.4.1.367 created 2019]

2.4.1.368

Accepted name:

oleanolate 3-O-glucosyltransferase

Reaction:

UDP-α-D-glucose + oleanolate = UDP + oleanolate 3-O-β-D-glucoside

Glossary:

oleanolate = 3β-hydroxyolean-12-en-28-oate

Other name(s):

UGT73C10 (gene name); UGT73C11 (gene name)

Systematic name:

UDP-α-D-glucose:oleanolate 3-O-glucosyltransferase

Comments:

The enzyme has been characterized from the saponin-producing crucifer plant Barbarea vulgaris.

Links to other databases:

References:

Augustin, J.M., Drok, S., Shinoda, T., Sanmiya, K., Nielsen, J.K., Khakimov, B., Olsen, C.E., Hansen, E.H., Kuzina, V., Ekstrom, C.T., Hauser, T. and Bak, S. UDP-glycosyltransferases from the UGT73C subfamily in Barbarea vulgaris catalyze sapogenin 3-O-glucosylation in saponin-mediated insect resistance. Plant Physiol. 160 (2012) 1881–1895. [PMID: 23027665]

[EC 2.4.1.368 created 2019]

2.5.1.152

Accepted name:

D-histidine 2-aminobutanoyltransferase

Reaction:

S-adenosyl-L-methionine + D-histidine = N-[(3S)-3-amino-3-carboxypropyl]-D-histidine + S-methyl-5′-thioadenosine

For diagram of staphylopine biosynthesis, click here

Glossary:

staphylopine = N-[(3S)-3-{[(1S)-1-carboxyethyl]amino}-3-carboxypropyl]-D-histidine

Other name(s):

cntL (gene name)

Systematic name:

S-adenosyl-L-methionine:D-histidine N-[(3S)-3-amino-3-carboxypropyl]-transferase

Comments:

The enzyme, characterized from the bacterium Staphylococcus aureus, participates in the biosynthesis of the metallophore staphylopine, which is involved in the acquisition of nickel, copper, and cobalt.

Links to other databases:

References:

Ghssein, G., Brutesco, C., Ouerdane, L., Fojcik, C., Izaute, A., Wang, S., Hajjar, C., Lobinski, R., Lemaire, D., Richaud, P., Voulhoux, R., Espaillat, A., Cava, F., Pignol, D., Borezee-Durant, E. and Arnoux, P. Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus. Science 352 (2016) 1105–1109. [PMID: 27230378]

[EC 2.5.1.152 created 2019]

2.6.1.115

Accepted name:

5-hydroxydodecatetraenal 1-aminotransferase

Reaction:

(2E,5S,6E,8E,10E)-1-aminododeca-2,6,8,10-tetraen-5-ol + pyruvate = (2E,5S,6E,8E,10E)-5-hydroxydodeca-2,6,8,10-tetraenal + L-alanine

For diagram of coelimycin A₁ biosynthesis, click here

Glossary:

coelimycin P1 = N-[(3R)-8-[(2E)-but-2-enoyl]-2-oxo-6-[(2E)-1,2,5,6-tetrahydropyridin-2-ylidene]-2,3,4,6-tetrahydro-1,5-oxathiocin-3-yl]acetamide

Other name(s):

cpkG (gene name)

Systematic name:

(2E,5S,6E,8E,10E)-1-aminododeca-2,6,8,10-tetraen-5-ol:pyruvate aminotransferase

Comments:

The enzyme, characterized from the bacterium Streptomyces coelicolor A₃(2), participates in the biosynthesis of coelimycin P1, where it catalyses the amination of (2E,5S,6E,8E,10E)-5-hydroxydodeca-2,6,8,10-tetraenal. L-glutamate can also serve as the amino group donor with lower efficiency.

Links to other databases:

References:

1.	Pawlik, K., Kotowska, M., Chater, K.F., Kuczek, K. and Takano, E. A cryptic type I polyketide synthase (cpk) gene cluster in Streptomyces coelicolor A3(2). Arch. Microbiol. 187 (2007) 87–99. [PMID: 17009021]
2.	Awodi, U.R., Ronan, J.L., Masschelein, J., Santos, E.LC. and Challis, G.L. Thioester reduction and aldehyde transamination are universal steps in actinobacterial polyketide alkaloid biosynthesis. Chem. Sci. 8 (2017) 411–415. [PMID: 28451186]

[EC 2.6.1.115 created 2019]

2.7.1.225

Accepted name:

L-serine kinase (ATP)

Reaction:

ATP + L-serine = ADP + O-phospho-L-serine

Other name(s):

sbnI (gene name)

Systematic name:

ATP:L-serine 3-phosphotransferase

Comments:

The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of L-2,3-diaminopropanoate, which is used by that organism as a precursor for the biosynthesis of the siderophore staphyloferrin B.

Links to other databases:

References:

1.	Verstraete, M.M., Perez-Borrajero, C., Brown, K.L., Heinrichs, D.E. and Murphy, M.EP. SbnI is a free serine kinase that generates O -phospho-l-serine for staphyloferrin B biosynthesis in Staphylococcus aureus. J. Biol. Chem. 293 (2018) 6147–6160. [PMID: 29483190]

[EC 2.7.1.225 created 2019]

2.7.1.226

Accepted name:

L-serine kinase (ADP)

Reaction:

ADP + L-serine = AMP + O-phospho-L-serine

For diagram of O³-acetyl-L-serine metabolism, click here

Other name(s):

serK (gene name)

Systematic name:

ADP:L-serine 3-phosphotransferase

Comments:

The enzyme, characterized in the hyperthermophilic archaeon Thermococcus kodakarensis, participates in L-cysteine biosynthesis.

Links to other databases:

References:

1.	Makino, Y., Sato, T., Kawamura, H., Hachisuka, S.I., Takeno, R., Imanaka, T. and Atomi, H. An archaeal ADP-dependent serine kinase involved in cysteine biosynthesis and serine metabolism. Nat. Commun. 7:13446 (2016). [PMID: 27857065]
2.	Nagata, R., Fujihashi, M., Kawamura, H., Sato, T., Fujita, T., Atomi, H. and Miki, K. Structural study on the reaction mechanism of a free serine kinase involved in cysteine biosynthesis. ACS Chem. Biol. 12 (2017) 1514–1523. [PMID: 28358477]

[EC 2.7.1.226 created 2019]

3.1.1.105

Accepted name:

3-O-acetylpapaveroxine carboxylesterase

Reaction:

3-O-acetylpapaveroxine + H₂O = narcotine hemiacetal + acetate

For diagram of noscapine biosynthesis, click here

Glossary:

3-O-acetylpapaveroxine = 6-{(S)-acetoxy[(5R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl]methyl}-2,3-dimethoxybenzaldehyde
narcotine hemiacetal = (3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-1,3-dihydroisobenzofuran-1-ol

Other name(s):

CXE1 (gene name)

Systematic name:

3-O-acetylpapaveroxine acetatehydrolase

Comments:

The enzyme, characterized from the plant Papaver somniferum (opium poppy), participates in the biosynthesis of the isoquinoline alkaloid noscapine.

Links to other databases:

References:

1.	Dang, T.T., Chen, X. and Facchini, P.J. Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nat. Chem. Biol. 11 (2015) 104–106. [DOI] [PMID: 25485687]
2.	Park, M.R., Chen, X., Lang, D.E., Ng, K.KS. and Facchini, P.J. Heterodimeric O-methyltransferases involved in the biosynthesis of noscapine in opium poppy. Plant J. 95 (2018) 252–267. [PMID: 29723437]

[EC 3.1.1.105 created 2019]

3.1.1.106

Accepted name:

O-acetyl-ADP-ribose deacetylase

Reaction:

(1) 3′′-O-acetyl-ADP-D-ribose + H₂O = ADP-D-ribose + acetate
(2) 2′′-O-acetyl-ADP-D-ribose + H₂O = ADP-D-ribose + acetate

Other name(s):

ymdB (gene name); MACROD1 (gene name)

Systematic name:

O-acetyl-ADP-D-ribose carboxylesterase

Comments:

The enzyme, characterized from the bacterium Escherichia coli and from human cells, removes the acetyl group from either the 2′′ or 3′′ position of O-acetyl-ADP-ribose, which are formed by the action of EC 2.3.1.286, protein acetyllysine N-acetyltransferase. The human enzyme can also remove ADP-D-ribose from phosphorylated double stranded DNA adducts.

Links to other databases:

References:

1.	Chen, D., Vollmar, M., Rossi, M.N., Phillips, C., Kraehenbuehl, R., Slade, D., Mehrotra, P.V., von Delft, F., Crosthwaite, S.K., Gileadi, O., Denu, J.M. and Ahel, I. Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. J. Biol. Chem. 286 (2011) 13261–13271. [PMID: 21257746]
2.	Zhang, W., Wang, C., Song, Y., Shao, C., Zhang, X. and Zang, J. Structural insights into the mechanism of Escherichia coli YmdB: A 2′-O-acetyl-ADP-ribose deacetylase. J. Struct. Biol. 192 (2015) 478–486. [PMID: 26481419]
3.	Agnew, T., Munnur, D., Crawford, K., Palazzo, L., Mikoc, A. and Ahel, I. MacroD1 is a promiscuous ADP-ribosyl hydrolase localized to mitochondria. Front. Microbiol. 9:20 (2018). [PMID: 29410655]

[EC 3.1.1.106 created 2019]

3.1.4.59

Accepted name:

cyclic-di-AMP phosphodiesterase

Reaction:

cyclic di-3′,5′-adenylate + H₂O = 5′-O-phosphonoadenylyl-(3′→5′)-adenosine

For diagram of cyclic di-3′,5′-adenylate biosynthesis and breakdown, click here

Glossary:

cyclic di-3′,5′-adenylate = cyclic bis(3′→5′)diadenylate
5′-O-phosphonoadenylyl-(3′→5′)-adenosine = pApA

Other name(s):

gdpP (gene name)

Systematic name:

cyclic bis(3′→5′)diadenylate 3′-adenylylhydrolase

Comments:

The enzyme, described from Gram-positive bacteria, degrades the second messenger cyclic di-3′,5′-adenylate. It is a membrane-bound protein that contains a cytoplasmic facing Per-Arnt-Sim (PAS) domain, a modified GGDEF domain, and a DHH/DHHA₁ domain, which confers the phosphodiesterase activity. Activity requires Mn²⁺ and is inhibited by pApA.

Links to other databases:

References:

1.	Rao, F., See, R.Y., Zhang, D., Toh, D.C., Ji, Q. and Liang, Z.X. YybT is a signaling protein that contains a cyclic dinucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity. J. Biol. Chem. 285 (2010) 473–482. [PMID: 19901023]
2.	Corrigan, R.M., Abbott, J.C., Burhenne, H., Kaever, V. and Grundling, A. c-di-AMP is a new second messenger in Staphylococcus aureus with a role in controlling cell size and envelope stress. PLoS Pathog. 7:e1002217 (2011). [PMID: 21909268]
3.	Griffiths, J.M. and O'Neill, A.J. Loss of function of the gdpP protein leads to joint β-lactam/glycopeptide tolerance in Staphylococcus aureus. Antimicrob. Agents Chemother. 56 (2012) 579–581. [PMID: 21986827]
4.	Bowman, L., Zeden, M.S., Schuster, C.F., Kaever, V. and Grundling, A. New insights into the cyclic di-adenosine monophosphate (c-di-AMP) degradation pathway and the requirement of the cyclic dinucleotide for acid stress resistance in Staphylococcus aureus. J. Biol. Chem. 291 (2016) 26970–26986. [PMID: 27834680]

[EC 3.1.4.59 created 2019]

3.1.4.60

Accepted name:

pApA phosphodiesterase

Reaction:

5′-O-phosphonoadenylyl-(3′→5′)-adenosine + H₂O = 2 AMP

For diagram of cyclic di-3′,5′-adenylate biosynthesis and breakdown, click here

Other name(s):

pde2 (gene name); pApA hydrolase

Systematic name:

5′-O-phosphonoadenylyl-(3′→5′)-adenosine phosphohydrolase

Comments:

The enzyme, characterized from the Gram-positive bacterium Staphylococcus aureus, is a cytoplasmic protein that contains a DHH/DHHA₁ domain. It can act on cyclic di-3′,5′-adenylate with a much lower activity (cf. EC 3.1.4.59, cyclic-di-AMP phosphodiesterase). Activity requires Mn²⁺ and is inhibited by ppGpp.

Links to other databases:

References:

1.	Bai, Y., Yang, J., Eisele, L.E., Underwood, A.J., Koestler, B.J., Waters, C.M., Metzger, D.W. and Bai, G. Two DHH subfamily 1 proteins in Streptococcus pneumoniae possess cyclic di-AMP phosphodiesterase activity and affect bacterial growth and virulence. J. Bacteriol. 195 (2013) 5123–5132. [PMID: 24013631]
2.	Ye, M., Zhang, J.J., Fang, X., Lawlis, G.B., Troxell, B., Zhou, Y., Gomelsky, M., Lou, Y. and Yang, X.F. DhhP, a cyclic di-AMP phosphodiesterase of Borrelia burgdorferi, is essential for cell growth and virulence. Infect. Immun. 82 (2014) 1840–1849. [PMID: 24566626]
3.	Tang, Q., Luo, Y., Zheng, C., Yin, K., Ali, M.K., Li, X. and He, J. Functional analysis of a c-di-AMP-specific phosphodiesterase MsPDE from Mycobacterium smegmatis. Int J Biol Sci 11 (2015) 813–824. [PMID: 26078723]
4.	Kuipers, K., Gallay, C., Martinek, V., Rohde, M., Martinkova, M., van der Beek, S.L., Jong, W.S., Venselaar, H., Zomer, A., Bootsma, H., Veening, J.W. and de Jonge, M.I. Highly conserved nucleotide phosphatase essential for membrane lipid homeostasis in Streptococcus pneumoniae. Mol. Microbiol. 101 (2016) 12–26. [PMID: 26691161]
5.	Bowman, L., Zeden, M.S., Schuster, C.F., Kaever, V. and Grundling, A. New insights into the cyclic di-adenosine monophosphate (c-di-AMP) degradation pathway and the requirement of the cyclic dinucleotide for acid stress resistance in Staphylococcus aureus. J. Biol. Chem. 291 (2016) 26970–26986. [PMID: 27834680]

[EC 3.1.4.60 created 2019]

*EC

3.2.1.15

Accepted name:

endo-polygalacturonase

Reaction:

(1,4-α-D-galacturonosyl)_n+m + H₂O = (1,4-α-D-galacturonosyl)_n + (1,4-α-D-galacturonosyl)_m

Other name(s):

pectin depolymerase (ambiguous); pectinase (ambiguous); endopolygalacturonase; pectolase (ambiguous); pectin hydrolase (ambiguous); pectin polygalacturonase (ambiguous); polygalacturonase (ambiguous); poly-α-1,4-galacturonide glycanohydrolase (ambiguous); endogalacturonase; endo-D-galacturonase; poly(1,4-α-D-galacturonide) glycanohydrolase (ambiguous)

Systematic name:

(1→4)-α-D-galacturonan glycanohydrolase (endo-cleaving)

Comments:

The enzyme catalyses the random hydrolysis of (1→4)-α-D-galactosiduronic linkages in pectate and other galacturonans. Different forms of the enzyme have different tolerances to methyl esterification of the substrate.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9032-75-1

References:

1.	Lineweaver, H. and Jansen, E.F. Pectic enzymes. Adv. Enzymol. Relat. Subj. Biochem. 11 (1951) 267–295.
2.	McCready, R.M. and Seegmiller, C.G. Action of pectic enzymes on oligogalacturonic acids and some of their derivatives. Arch. Biochem. Biophys. 50 (1954) 440–450. [DOI] [PMID: 13159344]
3.	Phaff, H.J. and Demain, A.L. The unienzymatic nature of yeast polygalacturonase. J. Biol. Chem. 218 (1956) 875–884. [PMID: 13295238]
4.	Deuel, H. and Stutz, E. Pectic substances and pectic enzymes. Adv. Enzymol. Relat. Areas Mol. Biol. 20 (1958) 341–382. [PMID: 13605988]
5.	Mill, P.J. and Tuttobello, R. The pectic enzymes of Aspergillus niger. 2. Endopolygalacturonase. Biochem. J. 79 (1961) 57–64. [PMID: 13770689]

[EC 3.2.1.15 created 1961, modified 2019]

*EC

3.2.1.67

Accepted name:

galacturonan 1,4-α-galacturonidase

Reaction:

[(1→4)-α-D-galacturonide]_n + H₂O = [(1→4)-α-D-galacturonide]_n-1 + D-galacturonate

Other name(s):

exo-polygalacturonase; poly(galacturonate) hydrolase (ambiguous); exo-D-galacturonase; exo-D-galacturonanase; exopoly-D-galacturonase; poly(1,4-α-D-galacturonide) galacturonohydrolase (ambiguous); pgaA (gene name); pgaB (gene name); pgaC (gene name); pgaD (gene name); pgaE (gene name); pgaI (gene name); pgaII (gene name); poly[(1→4)-α-D-galacturonide] galacturonohydrolase; galacturan 1,4-α-galacturonidase (incorrect)

Systematic name:

poly[(1→4)-α-D-galacturonide] non-reducing-end galacturonohydrolase

Comments:

The enzyme hydrolyses the first glycosidic bond from the non-reducing end of the substrate. It is specific for saturated oligomers of D-homogalacturonan, and is unable to degrade unsaturated substrates or methyl-esterified substrates.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9045-35-6

References:

1.	Hasegawa, H. and Nagel, C.W. Isolation of an oligogalacturonate hydrolase from a Bacillus species. Arch. Biochem. Biophys. 124 (1968) 513–520. [DOI] [PMID: 5661621]
2.	Kluskens, L.D., van Alebeek, G.J., Walther, J., Voragen, A.G., de Vos, W.M. and van der Oost, J. Characterization and mode of action of an exopolygalacturonase from the hyperthermophilic bacterium Thermotoga maritima. FEBS J. 272 (2005) 5464–5473. [PMID: 16262687]
3.	Martens-Uzunova, E.S., Zandleven, J.S., Benen, J.A., Awad, H., Kools, H.J., Beldman, G., Voragen, A.G., Van den Berg, J.A. and Schaap, P.J. A new group of exo-acting family 28 glycoside hydrolases of Aspergillus niger that are involved in pectin degradation. Biochem. J. 400 (2006) 43–52. [PMID: 16822232]
4.	Pijning, T., van Pouderoyen, G., Kluskens, L., van der Oost, J. and Dijkstra, B.W. The crystal structure of a hyperthermoactive exopolygalacturonase from Thermotoga maritima reveals a unique tetramer. FEBS Lett. 583 (2009) 3665–3670. [PMID: 19854184]

[EC 3.2.1.67 created 1972, modified 2019]

*EC

3.2.1.82

Accepted name:

exo-poly-α-digalacturonosidase

Reaction:

[(1→4)-α-D-galacturonosyl]_n + H₂O = α-D-galacturonosyl-(1→4)-D-galacturonate + [(1→4)-α-D-galacturonosyl]_n-2

Other name(s):

pehX (gene name); poly(1,4-α-D-galactosiduronate) digalacturonohydrolase; exopolygalacturonosidase (misleading); poly[(1→4)-α-D-galactosiduronate] digalacturonohydrolase; exo-poly-α-galacturonosidase

Systematic name:

poly[(1→4)-α-D-galactosiduronate] non-reducing-end-digalacturonohydrolase

Comments:

The enzyme, characterized from bacteria, hydrolyses the second α-1,4-glycosidic bond from the non-reducing end of polygalacturonate, releasing digalacturonate.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 37288-58-7

References:

1.	Hasegawa, H. and Nagel, C.W. Isolation of an oligogalacturonate hydrolase from a Bacillus species. Arch. Biochem. Biophys. 124 (1968) 513–520. [DOI] [PMID: 5661621]
2.	Hatanaka, C. and Ozawa, J. Enzymic degradation of pectic acid. XIII. New exopolygalacturonase producing digalacturonic acid from pectic acid. J. Agric. Chem. Soc. Jpn.. 43 (1968) 764–772.
3.	Hatanaka, C. and Ozawa, J. Ber. des O'Hara Inst. 15 (1971) 47.
4.	He, S.Y. and Collmer, A. Molecular cloning, nucleotide sequence, and marker exchange mutagenesis of the exo-poly-α-D-galacturonosidase-encoding pehX gene of Erwinia chrysanthemi EC16. J. Bacteriol. 172 (1990) 4988–4995. [PMID: 2168372]

[EC 3.2.1.82 created 1972, modified 2019]

*EC

3.4.19.13

Accepted name:

glutathione γ-glutamate hydrolase

Reaction:

(1) glutathione + H₂O = L-cysteinylglycine + L-glutamate
(2) a glutathione-S-conjugate + H₂O = an (L-cysteinylglycine)-S-conjugate + L-glutamate

Other name(s):

glutathionase; γ-glutamyltranspeptidase (ambiguous); glutathione hydrolase; GGT (gene name); ECM38 (gene name)

Comments:

This is a bifunctional protein that also has the activity of EC 2.3.2.2, γ-glutamyltransferase. The enzyme binds its substrate by forming an initial γ-glutamyl-enzyme intermediate, releasing the L-cysteinylglycine part of the molecule. The enzyme then reacts with either a water molecule or a different acceptor substrate (usually an L-amino acid or a dipeptide) to form L-glutamate or a product containing a new γ-glutamyl isopeptide bond, respectively. The enzyme acts on glutathione, glutathione-S-conjugates, and, at a lower level, on other substrates with an N-terminal L-γ-glutamyl residue. It plays a crucial part in the glutathione-mediated xenobiotic detoxification pathway. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide.

Links to other databases:

References:

1.	Hanigan, M.H. and Ricketts, W.A. Extracellular glutathione is a source of cysteine for cells that express γ-glutamyl transpeptidase. Biochemistry 32 (1993) 6302–6306. [PMID: 8099811]
2.	Carter, B.Z., Wiseman, A.L., Orkiszewski, R., Ballard, K.D., Ou, C.N. and Lieberman, M.W. Metabolism of leukotriene C₄ in γ-glutamyl transpeptidase-deficient mice. J. Biol. Chem. 272 (1997) 12305–12310. [DOI] [PMID: 9139674]
3.	Suzuki, H. and Kumagai, H. Autocatalytic processing of γ-glutamyltranspeptidase. J. Biol. Chem. 277 (2002) 43536–43543. [DOI] [PMID: 12207027]
4.	Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structures of γ-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc. Natl. Acad. Sci. USA 103 (2006) 6471–6476. [DOI] [PMID: 16618936]
5.	Boanca, G., Sand, A., Okada, T., Suzuki, H., Kumagai, H., Fukuyama, K. and Barycki, J.J. Autoprocessing of Helicobacter pylori γ-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad. J. Biol. Chem. 282 (2007) 534–541. [DOI] [PMID: 17107958]
6.	Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structure of the γ-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism. J. Biol. Chem. 282 (2007) 2433–2439. [DOI] [PMID: 17135273]
7.	Grzam, A., Martin, M.N., Hell, R. and Meyer, A.J. γ-Glutamyl transpeptidase GGT4 initiates vacuolar degradation of glutathione S-conjugates in Arabidopsis. FEBS Lett. 581 (2007) 3131–3138. [PMID: 17561001]
8.	Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208–214. [DOI] [PMID: 21447318]
9.	Keillor, J.W., Castonguay, R. and Lherbet, C. Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism. Methods Enzymol. 401 (2005) 449–467. [PMID: 16399402]

[EC 3.4.19.13 created 2011, modified 2019]

*EC

3.5.1.84

Accepted name:

biuret amidohydrolase

Reaction:

biuret + H₂O = urea-1-carboxylate + NH₃

For diagram of atrazine catabolism, click here

Glossary:

biuret = imidodicarbonic diamide
allophanate = urea-1-carboxylate

Other name(s):

biuH (gene name)

Systematic name:

biuret amidohydrolase

Comments:

The enzyme, characterized from the bacterium Rhizobium leguminosarum bv. viciae 3841, participates in the degradation of cyanuric acid, an intermediate in the degradation of s-triazide herbicides such as atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-1,3,5-triazine]. The substrate, biuret, forms by the spontaneous decarboxylation of 1-carboxybiuret in the absence of EC 3.5.1.131, 1-carboxybiuret hydrolase.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 95567-88-7

References:

1.	Cameron, S.M., Durchschein, K., Richman, J.E., Sadowsky, M.J. and Wackett, L.P. A new family of biuret hydrolases involved in s-triazine ring metabolism. ACS Catal. 2011 (2011) 1075–1082. [PMID: 21897878]
2.	Esquirol, L., Peat, T.S., Wilding, M., Lucent, D., French, N.G., Hartley, C.J., Newman, J. and Scott, C. Structural and biochemical characterization of the biuret hydrolase (BiuH) from the cyanuric acid catabolism pathway of Rhizobium leguminosarum bv. viciae 3841. PLoS One 13:e0192736 (2018). [PMID: 29425231]
3.	Esquirol, L., Peat, T.S., Wilding, M., Liu, J.W., French, N.G., Hartley, C.J., Onagi, H., Nebl, T., Easton, C.J., Newman, J. and Scott, C. An unexpected vestigial protein complex reveals the evolutionary origins of an s-triazine catabolic enzyme. J. Biol. Chem. 293 (2018) 7880–7891. [DOI] [PMID: 29523689]

[EC 3.5.1.84 created 2000, modified 2008, modified 2019]

3.5.1.130

Accepted name:

[amino group carrier protein]-lysine hydrolase

Reaction:

[amino group carrier protein]-C-terminal-γ-(L-lysyl)-L-glutamate + H₂O = [amino group carrier protein]-C-terminal-L-glutamate + L-lysine

Other name(s):

lysK (gene name)

Systematic name:

[amino group carrier protein]-C-terminal-γ-L-lysyl-L-glutamate amidohydrolase

Comments:

The enzyme participates in an L-lysine biosynthetic pathway in certain species of archaea and bacteria. In some organisms the enzyme also catalyses the activity of EC 3.5.1.132, [amino group carrier protein]-ornithine hydrolase.

Links to other databases:

References:

1.	Horie, A., Tomita, T., Saiki, A., Kono, H., Taka, H., Mineki, R., Fujimura, T., Nishiyama, C., Kuzuyama, T. and Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus. Nat. Chem. Biol. 5 (2009) 673–679. [DOI] [PMID: 19620981]
2.	Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277–283. [DOI] [PMID: 23434852]
3.	Yoshida, A., Tomita, T., Atomi, H., Kuzuyama, T. and Nishiyama, M. Lysine biosynthesis of Thermococcus kodakarensis with the capacity to function as an ornithine biosynthetic system. J. Biol. Chem. 291 (2016) 21630–21643. [DOI] [PMID: 27566549]
4.	Fujita, S., Cho, S.H., Yoshida, A., Hasebe, F., Tomita, T., Kuzuyama, T. and Nishiyama, M. Crystal structure of LysK, an enzyme catalyzing the last step of lysine biosynthesis in Thermus thermophilus, in complex with lysine: Insight into the mechanism for recognition of the amino-group carrier protein, LysW. Biochem. Biophys. Res. Commun. 491 (2017) 409–415. [DOI] [PMID: 28720495]

[EC 3.5.1.130 created 2019]

3.5.1.131

Accepted name:

1-carboxybiuret hydrolase

Reaction:

1-carboxybiuret + H₂O = urea-1,3-dicarboxylate + NH₃

For diagram of atrazine catabolism, click here

Glossary:

carboxybiuret = carbamoylcarbamoylcarbamic acid

Other name(s):

atzEG (gene names)

Systematic name:

1-carboxybiuret amidohydrolase

Comments:

The enzyme, characterized from the bacterium Pseudomonas sp. ADP, participates in the degradation of cyanuric acid, an intermediate in the degradation of s-triazine herbicides such as atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-1,3,5-triazine]. The enzyme is a heterotetramer composed of a catalytic subunit (AtzE) and an accessory subunit (AtzG) that stabilizes the complex.

Links to other databases:

References:

Esquirol, L., Peat, T.S., Wilding, M., Liu, J.W., French, N.G., Hartley, C.J., Onagi, H., Nebl, T., Easton, C.J., Newman, J. and Scott, C. An unexpected vestigial protein complex reveals the evolutionary origins of an s-triazine catabolic enzyme. J. Biol. Chem. 293 (2018) 7880–7891. [DOI] [PMID: 29523689]

[EC 3.5.1.131 created 2019]

3.5.1.132

Accepted name:

[amino group carrier protein]-ornithine hydrolase

Reaction:

[amino group carrier protein]-C-terminal-γ-(L-ornithyl)-L-glutamate + H₂O = [amino group carrier protein]-C-terminal-L-glutamate + L-ornithine

Other name(s):

lysK (gene name)

Systematic name:

[amino group carrier protein]-C-terminal-γ-L-ornithyl-L-glutamate amidohydrolase

Comments:

The enzyme participates in an L-arginine biosynthetic pathways in certain species of archaea and bacteria. In all cases known so far the enzyme also catalyses the activity of EC 3.5.1.130, [amino group carrier protein]-lysine hydrolase.

Links to other databases:

References:

1.	Ouchi, T., Tomita, T., Horie, A., Yoshida, A., Takahashi, K., Nishida, H., Lassak, K., Taka, H., Mineki, R., Fujimura, T., Kosono, S., Nishiyama, C., Masui, R., Kuramitsu, S., Albers, S.V., Kuzuyama, T. and Nishiyama, M. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus. Nat. Chem. Biol. 9 (2013) 277–283. [DOI] [PMID: 23434852]
2.	Yoshida, A., Tomita, T., Atomi, H., Kuzuyama, T. and Nishiyama, M. Lysine biosynthesis of Thermococcus kodakarensis with the capacity to function as an ornithine biosynthetic system. J. Biol. Chem. 291 (2016) 21630–21643. [DOI] [PMID: 27566549]

[EC 3.5.1.132 created 2019]

*EC

3.5.2.15

Accepted name:

cyanuric acid amidohydrolase

Reaction:

cyanuric acid + H₂O = 1-carboxybiuret

For diagram of atrazine catabolism, click here

Glossary:

cyanuric acid = 1,3,5-triazine-2,4,6(1H,3H,5H)-trione = 2,4,6-trihydroxy-s-triazine
1-carboxybiuret = N-[(carbamoylamino)carbonyl]carbamate

Other name(s):

atzD (gene name); trzD (gene name)

Systematic name:

cyanuric acid amidohydrolase

Comments:

The enzyme catalyses the ring cleavage of cyanuric acid, an intermediate in the degradation of s-triazide herbicides such as atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-1,3,5-triazine]. The enzyme is highly specific for cyanuric acid. The product was initially thought to be biuret, but was later shown to be 1-carboxybiuret.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 132965-78-7

References:

1.	Eaton, R.W. and Karns, J.S. Cloning and comparison of the DNA encoding ammelide aminohydrolase and cyanuric acid amidohydrolase from three s-triazine-degrading bacterial strains. J. Bacteriol. 173 (1991) 1363–1366. [DOI] [PMID: 1991731]
2.	Eaton, R.W. and Karns, J.S. Cloning and analysis of s-triazine catabolic genes from Pseudomonas sp. strain NRRLB-12227. J. Bacteriol. 173 (1991) 1215–1222. [DOI] [PMID: 1846859]
3.	Karns, J.S. Gene sequence and properties of an s-triazine ring-cleavage enzyme from Pseudomonas sp. strain NRRLB-12227. Appl. Environ. Microbiol. 65 (1999) 3512–3517. [DOI] [PMID: 10427042]
4.	Fruchey, I., Shapir, N., Sadowsky, M.J. and Wackett, L.P. On the origins of cyanuric acid hydrolase: purification, substrates, and prevalence of AtzD from Pseudomonas sp. strain ADP. Appl. Environ. Microbiol. 69 (2003) 3653–3657. [DOI] [PMID: 12788776]
5.	Esquirol, L., Peat, T.S., Wilding, M., Liu, J.W., French, N.G., Hartley, C.J., Onagi, H., Nebl, T., Easton, C.J., Newman, J. and Scott, C. An unexpected vestigial protein complex reveals the evolutionary origins of an s-triazine catabolic enzyme. J. Biol. Chem. 293 (2018) 7880–7891. [DOI] [PMID: 29523689]

[EC 3.5.2.15 created 2000, modified 2008, modified 2019]

3.6.3.16

Transferred entry:

arsenite-transporting ATPase. Now EC 7.3.2.7, arsenite-transporting ATPase

[EC 3.6.3.16 created 2000, deleted 2019]

3.6.3.17

Transferred entry:

monosaccharide-transporting ATPase. Now covered by various ABC-type monosaccharide transporters in sub-subclass EC 7.5.2.

[EC 3.6.3.17 created 2000, deleted 2019]

3.7.1.24

Accepted name:

2,4-diacetylphloroglucinol hydrolase

Reaction:

2,4-diacetylphloroglucinol + H₂O = 2-acetylphloroglucinol + acetate

Glossary:

phloroglucinol = benzene-1,3,5-triol
2,4-diacetylphloroglucinol = 1,1′-(2,4,6-trihydroxybenzene-1,3-diyl)diethan-1-one

Other name(s):

PhlG

Systematic name:

2,4-diacetylphloroglucinol acetylhydrolase

Comments:

Requires Zn²⁺. Isolated from the bacteria Pseudomonas fluorescens, Pseudomonas sp. YGJ3 and Mycobacterium abscessus 103. It reduces the antibiotic activity of 2,4-diacetylphloroglucinol.

Links to other databases:

References:

1.	Bottiglieri, M. and Keel, C. Characterization of PhlG, a hydrolase that specifically degrades the antifungal compound 2,4-diacetylphloroglucinol in the biocontrol agent Pseudomonas fluorescens CHA0. Appl. Environ. Microbiol. 72 (2006) 418–427. [PMID: 16391073]
2.	He, Y.X., Huang, L., Xue, Y., Fei, X., Teng, Y.B., Rubin-Pitel, S.B., Zhao, H. and Zhou, C.Z. Crystal structure and computational analyses provide insights into the catalytic mechanism of 2,4-diacetylphloroglucinol hydrolase PhlG from Pseudomonas fluorescens. J. Biol. Chem. 285 (2010) 4603–4611. [PMID: 20018877]
3.	Saitou, H., Watanabe, M. and Maruyama, K. Molecular and catalytic properties of 2,4-diacetylphloroglucinol hydrolase (PhlG) from Pseudomonas sp. YGJ3. Biosci. Biotechnol. Biochem. 76 (2012) 1239–1241. [PMID: 22790955]
4.	Zhang, Z., Jiang, Y.L., Wu, Y. and He, Y.X. Crystallization and preliminary X-ray diffraction analysis of a putative carbon-carbon bond hydrolase from Mycobacterium abscessus 103. Acta Crystallogr. F Struct. Biol. Commun. 71 (2015) 239–242. [PMID: 25664803]

[EC 3.7.1.24 created 2019]

3.7.1.25

Accepted name:

2-hydroxy-6-oxohepta-2,4-dienoate hydrolase

Reaction:

(2Z,4E)-2-hydroxy-6-oxohepta-2,4-dienoate + H₂O = (2Z)-2-hydroxypenta-2,4-dienoate + acetate

Other name(s):

todF (gene name)

Systematic name:

(2Z,4E)-2-hydroxy-6-oxohepta-2,4-dienoate acetylhydrolase

Comments:

A bacterial enzyme that participates in the degradation of toluene and 2-nitrotoluene.

Links to other databases:

References:

1.	Kukor, J.J. and Olsen, R.H. Genetic organization and regulation of a meta cleavage pathway for catechols produced from catabolism of toluene, benzene, phenol, and cresols by Pseudomonas pickettii PKO1. J. Bacteriol. 173 (1991) 4587–4594. [PMID: 1856161]
2.	Menn, F.M., Zylstra, G.J. and Gibson, D.T. Location and sequence of the todF gene encoding 2-hydroxy-6-oxohepta-2,4-dienoate hydrolase in Pseudomonas putida F1. Gene 104 (1991) 91–94. [PMID: 1916282]
3.	Haigler, B.E., Wallace, W.H. and Spain, J.C. Biodegradation of 2-nitrotoluene by Pseudomonas sp. strain JS42. Appl. Environ. Microbiol. 60 (1994) 3466–3469. [PMID: 7944378]

[EC 3.7.1.25 created 2019]

4.1.1.70

Transferred entry:

glutaconyl-CoA decarboxylase. Now EC 7.2.4.5, glutaconyl-CoA decarboxylase

[EC 4.1.1.70 created 1986, modified 2003, deleted 2019]

4.1.1.115

Accepted name:

indoleacetate decarboxylase

Reaction:

(1H-indol-3-yl)acetate = skatole + CO₂

For diagram of indoleacetic acid biosynthesis, click here

Glossary:

(1H-indol-3-yl)acetate = indoleacetate
skatole = 3-methyl-1H-indole

Other name(s):

IAD

Systematic name:

(1H-indol-3-yl)acetate carboxy-lyase (skatole-forming)

Comments:

This glycyl radical enzyme has been isolate from a number of bacterial species. Skatole contributes to the characteristic smell of animal faeces.

Links to other databases:

References:

1.	Liu, D., Wei, Y., Liu, X., Zhou, Y., Jiang, L., Yin, J., Wang, F., Hu, Y., Nanjaraj Urs, A.N., Liu, Y., Ang, E.L., Zhao, S., Zhao, H. and Zhang, Y. Indoleacetate decarboxylase is a glycyl radical enzyme catalysing the formation of malodorant skatole. Nat. Commun. 9:4224 (2018). [PMID: 30310076]

[EC 4.1.1.115 created 2019]

4.1.1.116

Accepted name:

D-ornithine/D-lysine decarboxylase

Reaction:

(1) D-ornithine = putrescine + CO₂
(2) D-lysine = cadaverine + CO₂

For diagram of spermine biosynthesis, click here

Glossary:

cadaverine = pentane-1,5-diamine
putrescine = butane-1,4-diamine

Other name(s):

dokD (gene name); DOKDC

Systematic name:

D-ornithine/D-lysine carboxy-lyase

Comments:

The enzyme, characterized from the bacterium Salmonella typhimurium LT2, is specific for D-ornithine and D-lysine. Requires pyridoxal 5′-phosphate.

Links to other databases:

References:

1.	Phillips, R.S., Poteh, P., Miller, K.A. and Hoover, T.R. STM2360 encodes a D-ornithine/D-lysine decarboxylase in Salmonella enterica serovar typhimurium. Arch. Biochem. Biophys. 634 (2017) 83–87. [PMID: 29024617]

[EC 4.1.1.116 created 2019]

4.1.1.117

Accepted name:

2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate decarboxylase

Reaction:

2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate = 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate + CO₂

Glossary:

staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate

Other name(s):

sbnH (gene name)

Systematic name:

2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate carboxy-lyase (2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate-forming)

Comments:

The enzyme, characterized from the bacterium Staphylococcus aureus, participates in the biosynthesis of the siderophore staphyloferrin B.

Links to other databases:

References:

1.	Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248]

[EC 4.1.1.117 created 2019]

*EC

4.2.1.139

Accepted name:

pterocarpan synthase

Reaction:

a (4R)-4,2′-dihydroxyisoflavan = a pterocarpan + H₂O

For diagram of medicarpin and formononetin derivatives biosynthesis, click here

Glossary:

an isoflavan = an isoflavonoid with a 3,4-dihydro-3-aryl-2H-1-benzopyran skeleton.
(–)-medicarpin = (6aR,11aR)-9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol
(+)-medicarpin = (6aS,11aS)-9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromen-3-ol
(–)-maackiain = (6aR,12aR)-6a,12a-dihydro-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-3-ol
(+)-maackiain = (6aS,12aS)-6a,12a-dihydro-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-3-ol
(+)-pterocarpan = (6aR,11aR)-6a,11a-dihydro-6H-[1]benzofuran[3,2-c][1]benzopyran

Other name(s):

medicarpin synthase; medicarpan synthase; 7,2′-dihydroxy-4′-methoxyisoflavanol dehydratase; 2′,7-dihydroxy-4′-methoxyisoflavanol dehydratase; DMI dehydratase; DMID; 2′-hydroxyisoflavanol 4,2′-dehydratase; PTS (gene name); 4′-methoxyisoflavan-2′,4,7-triol hydro-lyase [(–)-medicarpin-forming]

Systematic name:

(4R)-4,2′-dihydroxyisoflavan hydro-lyase (pterocarpan-forming)

Comments:

The enzyme catalyses the formation of the additional ring in pterocarpan, the basic structure of phytoalexins produced by leguminous plants, including (–)-medicarpin, (+)-medicarpin, (–)-maackiain and (+)-maackiain. The enzyme requires that the hydroxyl group at C-4 of the substrate is in the (4R) configuration. The configuration of the hydrogen atom at C-3 determines whether the pterocarpan is the (+)- or (–)-enantiomer. The enzyme contains amino acid motifs characteristic of dirigent proteins.

Links to other databases:

References:

1.	Guo, L., Dixon, R.A. and Paiva, N.L. The ‘pterocarpan synthase’ of alfalfa: association and co-induction of vestitone reductase and 7,2′-dihydroxy-4′-methoxy-isoflavanol (DMI) dehydratase, the two final enzymes in medicarpin biosynthesis. FEBS Lett. 356 (1994) 221–225. [DOI] [PMID: 7805842]
2.	Guo, L., Dixon, R.A. and Paiva, N.L. Conversion of vestitone to medicarpin in alfalfa (Medicago sativa L.) is catalyzed by two independent enzymes. Identification, purification, and characterization of vestitone reductase and 7,2′-dihydroxy-4′-methoxyisoflavanol dehydratase. J. Biol. Chem. 269 (1994) 22372–22378. [PMID: 8071365]
3.	Uchida, K., Akashi, T. and Aoki, T. The missing link in leguminous pterocarpan biosynthesis is a dirigent domain-containing protein with isoflavanol dehydratase activity. Plant Cell Physiol. 58 (2017) 398–408. [PMID: 28394400]

[EC 4.2.1.139 created 2013, modified 2019]

4.2.3.201

Accepted name:

hydropyrene synthase

Reaction:

geranylgeranyl diphosphate = hydropyrene + diphosphate

For mechanism, click here and for diagram of miscellaneous diterpenoid biosynthesis, click here

Glossary:

hydropyrene = (1R,3aR,3a¹R,5aR,5a¹S,8aS,10aS)-1,5a,8a-trimethyl-4-methylidenehexadecahydropyrene

Other name(s):

HpS

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, hydropyrene-forming)

Comments:

Isolated from the bacterium Streptomyces clavuligerus. The 1-proR hydrogen atom of geranylgeranyl diphosphate is lost in the reaction. The enzyme also produces hydropyrenol, isoelisabethatriene and traces of other diterpenoids. cf. EC 4.2.3.202, hydropyrenol synthase, and EC 4.2.3.203, isoelisabethatriene synthase.

Links to other databases:

References:

1.	Rinkel, J., Rabe, P., Chen, X., Kollner, T.G., Chen, F. and Dickschat, J.S. Mechanisms of the diterpene cyclases β-pinacene synthase from Dictyostelium discoideum and hydropyrene synthase from Streptomyces clavuligerus. Chem. Eur. J. 23 (2017) 10501–10505. [PMID: 28696553]

[EC 4.2.3.201 created 2019]

4.2.3.202

Accepted name:

hydropyrenol synthase

Reaction:

geranylgeranyl diphosphate + H₂O = hydropyrenol + diphosphate

For mechanism, click here and for diagram of miscellaneous diterpenoid biosynthesis, click here

Glossary:

hydropyrenol = (1R,3aR,3a¹S,4S,5aR,5a¹S,8aS,10aS)-1,4,5a,8a-tetramethylhexadecahydropyren-4-ol

Other name(s):

HpS

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, hydropyrenol-forming)

Comments:

Isolated from the bacterium Streptomyces clavuligerus. The 1-proR hydrogen atom of geranylgeranyl diphosphate is lost in the reaction. The enzyme also produces hydropyrene, isoelisabethatriene and traces of other diterpenoids. cf. EC 4.2.3.201, hydropyrene synthase, and EC 4.2.3.203, isoelisabethatriene synthase.

Links to other databases:

References:

1.	Rinkel, J., Rabe, P., Chen, X., Kollner, T.G., Chen, F. and Dickschat, J.S. Mechanisms of the diterpene cyclases β-pinacene synthase from Dictyostelium discoideum and hydropyrene synthase from Streptomyces clavuligerus. Chem. Eur. J. 23 (2017) 10501–10505. [PMID: 28696553]

[EC 4.2.3.202 created 2019]

4.2.3.203

Accepted name:

isoelisabethatriene synthase

Reaction:

geranylgeranyl diphosphate = isoelisabethatriene + diphosphate

For mechanism, click here and for diagram of miscellaneous diterpenoid biosynthesis, click here

Glossary:

isoelisabethatriene = (1S,4R)-4,7-dimethyl-1-[(2R)-6-methylhept-5-en-2-yl]-1,2,3,4,5,6-hexahydronaphthalene

Other name(s):

HpS (ambiguous)

Systematic name:

geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, isoelisabethatriene-forming)

Comments:

Isolated from the bacterium Streptomyces clavuligerus. The 1-proR hydrogen atom of geranylgeranyl diphosphate is involved in a 1,3-hydride shift to the side-chain. The enzyme also produces hydropyrene, hydropyrenol, and traces of other diterpenoids. cf. EC 4.2.3.201, hydropyrene synthase, and EC 4.2.3.202, hydropyrenol synthase.

Links to other databases:

References:

1.	Rinkel, J., Rabe, P., Chen, X., Kollner, T.G., Chen, F. and Dickschat, J.S. Mechanisms of the diterpene cyclases β-pinacene synthase from Dictyostelium discoideum and hydropyrene synthase from Streptomyces clavuligerus. Chem. Eur. J. 23 (2017) 10501–10505. [PMID: 28696553]

[EC 4.2.3.203 created 2019]

4.2.99.24

Accepted name:

thebaine synthase

Reaction:

salutaridinol 7-O-acetate = thebaine + acetate

For diagram of thebaine biosynthesis, click here

Other name(s):

THS

Systematic name:

salutaridinol 7-O-acetate acetate-lyase (thebaine-forming)

Comments:

Isolated from the plant Papaver somniferum (opium poppy). The reaction occurs spontaneously when the pH is between 8-9, but the enzyme is required at the physiological pH, which is close to 7.

Links to other databases:

References:

Chen, X., Hagel, J.M., Chang, L., Tucker, J.E., Shiigi, S.A., Yelpaala, Y., Chen, H.Y., Estrada, R., Colbeck, J., Enquist-Newman, M., Ibanez, A.B., Cottarel, G., Vidanes, G.M. and Facchini, P.J. A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis. Nat. Chem. Biol. 14 (2018) 738–743. [PMID: 29807982]

[EC 4.2.99.24 created 2019]

5.1.1.24

Accepted name:

histidine racemase

Reaction:

L-histidine = D-histidine

For diagram of staphylopine biosynthesis, click here

Glossary:

staphylopine = (2S)-4-{[(1R)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}-2-[(1-carboxyethyl)amino]butanoate

Other name(s):

cntK (gene name)

Systematic name:

histidine racemase

Comments:

Links to other databases:

References:

[EC 5.1.1.24 created 2019]

5.1.3.43

Accepted name:

sulfoquinovose mutarotase

Reaction:

6-sulfo-α-D-quinovose = 6-sulfo-β-D-quinovose

Systematic name:

6-sulfo-D-quinovose 1-epimerase

Comments:

The enzyme is found in bacteria that possess sulfoglycolytic pathways. The enzyme can also act on other aldohexoses such as D-galactose, D-glucose, D-glucose-6-phosphate, and D-glucuronate, but with lower efficiency. Does not act on D-mannose.

Links to other databases:

References:

1.	Abayakoon, P., Lingford, J.P., Jin, Y., Bengt, C., Davies, G.J., Yao, S., Goddard-Borger, E.D. and Williams, S.J. Discovery and characterization of a sulfoquinovose mutarotase using kinetic analysis at equilibrium by exchange spectroscopy. Biochem. J. 475 (2018) 1371–1383. [PMID: 29535276]

[EC 5.1.3.43 created 2019]

*EC

6.2.1.40

Accepted name:

4-hydroxybutyrate—CoA ligase (AMP-forming)

Reaction:

ATP + 4-hydroxybutanoate + CoA = AMP + diphosphate + 4-hydroxybutanoyl-CoA

For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Other name(s):

4-hydroxybutyrate-CoA synthetase (ambiguous); 4-hydroxybutyrate:CoA ligase (ambiguous); hbs (gene name); 4-hydroxybutyrate—CoA ligase

Systematic name:

4-hydroxybutanoate:CoA ligase (AMP-forming)

Comments:

Isolated from the archaeon Metallosphaera sedula. Involved in the 3-hydroxypropanoate/4-hydroxybutanoate cycle. cf. EC 6.2.1.56, 4-hydroxybutyrate—CoA ligase (ADP-forming).

Links to other databases:

References:

1.	Ramos-Vera, W.H., Weiss, M., Strittmatter, E., Kockelkorn, D. and Fuchs, G. Identification of missing genes and enzymes for autotrophic carbon fixation in crenarchaeota. J. Bacteriol. 193 (2011) 1201–1211. [DOI] [PMID: 21169482]
2.	Hawkins, A.S., Han, Y., Bennett, R.K., Adams, M.W. and Kelly, R.M. Role of 4-hydroxybutyrate-CoA synthetase in the CO₂ fixation cycle in thermoacidophilic archaea. J. Biol. Chem. 288 (2013) 4012–4022. [DOI] [PMID: 23258541]

[EC 6.2.1.40 created 2014, modified 2019]

6.2.1.56

Accepted name:

4-hydroxybutyrate—CoA ligase (ADP-forming)

Reaction:

ATP + 4-hydroxybutanoate + CoA = ADP + phosphate + 4-hydroxybutanoyl-CoA

For diagram of the 3-hydroxypropanoate/4-hydroxybutanoate cycle and dicarboxylate/4-hydroxybutanoate cycle in archaea, click here

Other name(s):

Nmar_0206 (locus name)

Systematic name:

4-hydroxybutanoate:CoA ligase (ADP-forming)

Comments:

The enzyme, characterized from the marine ammonia-oxidizing archaeon Nitrosopumilus maritimus, participates in a variant of the 3-hydroxypropanoate/4-hydroxybutanate CO₂ fixation cycle. cf. EC 6.2.1.40, 4-hydroxybutyrate—CoA ligase (AMP-forming).

Links to other databases:

References:

Konneke, M., Schubert, D.M., Brown, P.C., Hugler, M., Standfest, S., Schwander, T., Schada von Borzyskowski, L., Erb, T.J., Stahl, D.A. and Berg, I.A. Ammonia-oxidizing archaea use the most energy-efficient aerobic pathway for CO₂ fixation. Proc. Natl. Acad. Sci. USA 111 (2014) 8239–8244. [PMID: 24843170]

[EC 6.2.1.56 created 2019]

6.2.1.57

Accepted name:

long-chain fatty acid adenylase/transferase FadD23

Reaction:

(1) ATP + stearate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + diphosphate + a stearoyl-[(hydroxy)phthioceranic acid synthase] (overall reaction)
(1a) ATP + stearate = diphosphate + (stearoyl)adenylate
(1b) (stearoyl)adenylate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + a stearoyl-[(hydroxy)phthioceranic acid synthase]
(2) ATP + palmitate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + diphosphate + a palmitoyl-[(hydroxy)phthioceranic acid synthase] (overall reaction)
(2a) ATP + palmitate = diphosphate + (palmitoyl)adenylate
(2b) (palmitoyl)adenylate + a holo-[(hydroxy)phthioceranic acid synthase] = AMP + a palmitoyl-[(hydroxy)phthioceranic acid synthase]

Other name(s):

fadD23 (gene name); long-chain fatty acid adenylyltransferase FadD23

Systematic name:

palmitate:holo-[(hydroxy)phthioceranic acid synthase] ligase

Comments:

This mycobacterial enzyme activates palmitate and stearate by adenylation, followed by their loading onto the polyketide synthase EC 2.3.1.287, phthioceranic/hydroxyphthioceranic acid synthase.

Links to other databases:

References:

1.	Gokhale, R.S., Saxena, P., Chopra, T. and Mohanty, D. Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. Nat. Prod. Rep. 24 (2007) 267–277. [PMID: 17389997]
2.	Lynett, J. and Stokes, R.W. Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages. Microbiology 153 (2007) 3133–3140. [PMID: 17768256]

[EC 6.2.1.57 created 2019]

*EC

6.3.2.38

Accepted name:

N²-citryl-N⁶-acetyl-N⁶-hydroxylysine synthase

Reaction:

2 ATP + citrate + N⁶-acetyl-N⁶-hydroxy-L-lysine + H₂O = 2 ADP + 2 phosphate + N⁶-acetyl-N²-citryl-N⁶-hydroxy-L-lysine

For diagram of aerobactin biosynthesis, click here

Glossary:

citryl = 3-hydroxy-3,4-dicarboxybutanoyl

Other name(s):

N^α-citryl-N^ε-acetyl-N^ε-hydroxylysine synthase; iucA (gene name)

Systematic name:

citrate:N⁶-acetyl-N⁶-hydroxy-L-lysine ligase (AMP-forming)

Comments:

Requires Mg²⁺. The enzyme is involved in the biosynthesis of aerobactin, a dihydroxamate siderophore. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme is believed to form an adenylate intermediate prior to ligation.

Links to other databases:

References:

1.	Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [DOI] [PMID: 4313071]
2.	Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N⁶-acetyl-N⁶-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101.
3.	de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [DOI] [PMID: 2935523]
4.	Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443.
5.	Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [DOI] [PMID: 15719346]
6.	Oves-Costales, D., Kadi, N. and Challis, G.L. The long-overlooked enzymology of a nonribosomal peptide synthetase-independent pathway for virulence-conferring siderophore biosynthesis. Chem. Commun. (Camb.) (2009) 6530–6541. [PMID: 19865642]

[EC 6.3.2.38 created 2012, modified 2019]

*EC

6.3.2.39

Accepted name:

aerobactin synthase

Reaction:

ATP + N²-citryl-N⁶-acetyl-N⁶-hydroxy-L-lysine + N⁶-acetyl-N⁶-hydroxy-L-lysine = AMP + diphosphate + aerobactin

For diagram of aerobactin biosynthesis, click here

Other name(s):

iucC (gene name)

Systematic name:

N²-citryl-N⁶-acetyl-N⁶-hydroxy-L-lysine:N⁶-acetyl-N⁶-hydroxy-L-lysine ligase (AMP-forming)

Comments:

Requires Mg²⁺. The enzyme is involved in the biosynthesis of aerobactin, a dihydroxamate siderophore. It belongs to a class of siderophore synthases known as type C nonribosomal peptide synthase-independent synthases (NIS). Type C enzymes are responsible for the formation of amide or ester bonds between a variety of substrates and a prochiral carboxyl group of a citrate molecule that is already linked to a different moiety at its other prochiral carboxyl group. The enzyme is believed to form an adenylate intermediate prior to ligation.

Links to other databases:

References:

1.	Gibson, F. and Magrath, D.I. The isolation and characterization of a hydroxamic acid (aerobactin) formed by Aerobacter aerogenes 62-I. Biochim. Biophys. Acta 192 (1969) 175–184. [DOI] [PMID: 4313071]
2.	Maurer, P.J. and Miller, M. Microbial iron chelators: total synthesis of aerobactin and its constituent amino acid, N⁶-acetyl-N⁶-hydroxylysine. J. Am. Chem. Soc. 104 (1982) 3096–3101.
3.	Appanna, D.L., Grundy, B.J., Szczepan, E.W. and Viswanatha, T. Aerobactin synthesis in a cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 801 (1984) 437–443.
4.	de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570–578. [DOI] [PMID: 2935523]
5.	de Lorenzo, V. and Neilands, J.B. Characterization of iucA and iucC genes of the aerobactin system of plasmid ColV-K30 in Escherichia coli. J. Bacteriol. 167 (1986) 350–355. [DOI] [PMID: 3087960]
6.	Challis, G.L. A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases. ChemBioChem 6 (2005) 601–611. [DOI] [PMID: 15719346]
7.	Oves-Costales, D., Kadi, N. and Challis, G.L. The long-overlooked enzymology of a nonribosomal peptide synthetase-independent pathway for virulence-conferring siderophore biosynthesis. Chem. Commun. (Camb.) (2009) 6530–6541. [PMID: 19865642]

[EC 6.3.2.39 created 2012, modified 2019]

6.3.2.54

Accepted name:

L-2,3-diaminopropanoate—citrate ligase

Reaction:

ATP + L-2,3-diaminopropanoate + citrate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate

Glossary:

staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate

Other name(s):

sbnE (gene name); 2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate synthtase

Systematic name:

L-2,3-diaminopropanoate:citrate ligase (2-[(L-alanin-3-ylcarbamoyl)methyl]-2-hydroxybutanedioate-forming)

Comments:

Requires Mg²⁺. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation.

Links to other databases:

References:

1.	Dale, S.E., Doherty-Kirby, A., Lajoie, G. and Heinrichs, D.E. Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Infect. Immun. 72 (2004) 29–37. [PMID: 14688077]
2.	Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248]

[EC 6.3.2.54 created 2019]

6.3.2.55

Accepted name:

2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate synthase

Reaction:

ATP + 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate + L-2,3-diaminopropanoate = AMP + diphosphate + 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate

For diagram of staphyloferrin B biosynthesis, click here

Glossary:

staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate

Other name(s):

sbnF (gene name)

Systematic name:

2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate:L-2,3-diaminopropanoate ligase {2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate-forming}

Comments:

Requires Mg²⁺. The enzyme, characterized from the bacterium Staphylococcus aureus, is involved in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type C nonribosomal peptide synthase-independent synthases (NIS). Type C NIS enzymes recognize esterified or amidated derivatives of carboxylic acids. The enzyme likely forms a 2-[(2-aminoethylcarbamoyl)methyl]-2-hydroxybutanedioate adenylate intermediate prior to ligation.

Links to other databases:

References:

1.	Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248]

[EC 6.3.2.55 created 2019]

6.3.2.56

Accepted name:

staphyloferrin B synthase

Reaction:

ATP + 2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate + 2-oxoglutarate = AMP + diphosphate + staphyloferrin B

For diagram of staphyloferrin B biosynthesis, click here

Glossary:

staphyloferrin B = 5-[(2-{[(3S)-5-{[(2S)-2-amino-2-carboxyethyl]amino}-3-carboxy-3-hydroxy-5-oxopentanoyl]amino}ethyl)amino]-2,5-dioxopentanoate

Other name(s):

sbnC (gene name)

Systematic name:

2-[(L-alanin-3-ylcarbamoyl)methyl]-3-(2-aminoethylcarbamoyl)-2-hydroxypropanoate:2-oxoglutarate ligase (staphyloferrin B-forming)

Comments:

Requires Mg²⁺. The enzyme, characterized from the bacterium Staphylococcus aureus, catalyses the last step in the biosynthesis of the siderophore staphyloferrin B. It belongs to a class of siderophore synthases known as type B nonribosomal peptide synthase-independent synthases (NIS). Type B NIS enzymes recognize the δ-acid group of 2-oxoglutarate. The enzyme forms a 2-oxoglutarate adenylate intermediate prior to ligation.

Links to other databases:

References:

1.	Cheung, J., Beasley, F.C., Liu, S., Lajoie, G.A. and Heinrichs, D.E. Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus. Mol. Microbiol. 74 (2009) 594–608. [PMID: 19775248]

[EC 6.3.2.56 created 2019]

6.3.2.57

Accepted name:

staphyloferrin A synthase

Reaction:

ATP + N⁵-[(S)-citryl]-D-ornithine + citrate = AMP + diphosphate + staphyloferrin A

For diagram of staphyloferrin A biosynthesis, click here

Glossary:

staphyloferrin A = N²-[(R)-citryl],N⁵-[(S)-citryl]-D-ornithine
citryl = 3-hydroxy-3,4-dicarboxybutanoyl

Other name(s):

sfnaB (gene name)

Systematic name:

N⁵-[(S)-citryl]-D-ornithine:citrate ligase (staphyloferrin A-forming)

Comments:

Requires Mg²⁺. The enzyme, characterized from the bacterium Staphylococcus aureus, catalyses the last step in the biosynthesis of the siderophore staphyloferrin A. It belongs to a class of siderophore synthases known as type A nonribosomal peptide synthase-independent synthases (NIS). Type A NIS enzymes are responsible for the formation of amide or ester bonds between polyamines or amino alcohols and a prochiral carboxyl group of citrate. The enzyme forms a citrate adenylate intermediate prior to ligation.

Links to other databases:

References:

1.	Cotton, J.L., Tao, J. and Balibar, C.J. Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A. Biochemistry 48 (2009) 1025–1035. [PMID: 19138128]

[EC 6.3.2.57 created 2019]

*EC

6.3.5.6

Accepted name:

asparaginyl-tRNA synthase (glutamine-hydrolysing)

Reaction:

ATP + L-aspartyl-tRNA^Asn + L-glutamine + H₂O = ADP + phosphate + L-asparaginyl-tRNA^Asn + L-glutamate
(1a) L-glutamine + H₂O = L-glutamate + NH₃
(1b) ATP + L-aspartyl-tRNA^Asn = ADP + 4-phosphooxy-L-aspartyl-tRNA^Asn
(1c) 4-phosphooxy-L-aspartyl-tRNA^Asn + NH₃ = L-asparaginyl-tRNA^Asn + phosphate

Other name(s):

Asp-AdT; Asp-tRNA^Asn amidotransferase; aspartyl-tRNA^Asn amidotransferase; Asn-tRNA^Asn:L-glutamine amido-ligase (ADP-forming); aspartyl-tRNA^Asn:L-glutamine amido-ligase (ADP-forming); GatCAB

Systematic name:

L-aspartyl-tRNA^Asn:L-glutamine amido-ligase (ADP-forming)

Comments:

This reaction forms part of a two-reaction system for producing asparaginyl-tRNA in Deinococcus radiodurans and other organisms lacking a specific enzyme for asparagine synthesis. In the first step, a non-discriminating ligase (EC 6.1.1.23, aspartate—tRNA^Asn ligase) mischarges tRNA^Asn with aspartate, leading to the formation of aspartyl-tRNA^Asn. The aspartyl-tRNA^Asn is not used in protein synthesis until the present enzyme converts it into asparaginyl-tRNA^Asn (aspartyl-tRNA^Asp is not a substrate for this enzyme). A glutaminase subunit (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is transferred by a 30 Å tunnel to a synthase subunit, where it is ligated to the carboxy group that has been activated by phosphorylation. Bacterial GatCAB complexes also has the activity of EC 6.3.5.7 [glutaminyl-tRNA synthase (glutamine-hydrolysing)].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, CAS registry number: 37211-76-0

References:

1.	Curnow, A.W., Tumbula, D.L., Pelaschier, J.T., Min, B. and Söll, D. Glutamyl-tRNA^Gln amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 12838–12843. [DOI] [PMID: 9789001]
2.	Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617–650. [DOI] [PMID: 10966471]
3.	Min, B., Pelaschier, J.T., Graham, D.E., Tumbula-Hansen, D. and Söll, D. Transfer RNA-dependent amino acid biosynthesis: an essential route to asparagine formation. Proc. Natl. Acad. Sci. USA 99 (2002) 2678–2683. [DOI] [PMID: 11880622]

[EC 6.3.5.6 created 2002, modified 2012, modified 2019]

*EC

6.3.5.7

Accepted name:

glutaminyl-tRNA synthase (glutamine-hydrolysing)

Reaction:

ATP + L-glutamyl-tRNA^Gln + L-glutamine = ADP + phosphate + L-glutaminyl-tRNA^Gln + L-glutamate (overall reaction)
(1a) L-glutamine + H₂O = L-glutamate + NH₃
(1b) ATP + L-glutamyl-tRNA^Gln = ADP + 5-phosphooxy-L-glutamyl-tRNA^Gln
(1c) 5-phosphooxy-L-glutamyl-tRNA^Gln + NH₃ = L-glutaminyl-tRNA^Gln + phosphate

Other name(s):

Glu-AdT; Glu-tRNA^Gln amidotransferase; glutamyl-tRNA^Gln amidotransferase; Glu-tRNA^Gln:L-glutamine amido-ligase (ADP-forming); GatCAB; GatFAB; GatDE

Systematic name:

L-glutamyl-tRNA^Gln:L-glutamine amido-ligase (ADP-forming)

Comments:

In systems lacking discernible glutamine—tRNA ligase (EC 6.1.1.18), glutaminyl-tRNA^Gln is formed by a two-enzyme system. In the first step, a nondiscriminating ligase (EC 6.1.1.24, glutamate—tRNA^Gln ligase) mischarges tRNA^Gln with glutamate, forming glutamyl-tRNA^Gln. The glutamyl-tRNA^Gln is not used in protein synthesis until the present enzyme converts it into glutaminyl-tRNA^Gln (glutamyl-tRNA^Glu is not a substrate for this enzyme). A glutaminase subunit (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is transferred by a 30 Å tunnel to a synthase subunit, where it is ligated to the carboxy group that has been activated by phosphorylation. Some bacterial GatCAB complexes also has the activity of EC 6.3.5.6 [asparaginyl-tRNA synthase (glutamine-hydrolysing)].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 52232-48-1

References:

1.	Curnow, A.W., Tumbula, D.L., Pelaschier, J.T., Min, B. and Söll, D. Glutamyl-tRNA^Gln amidotransferase in Deinococcus radiodurans may be confined to asparagine biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 12838–12843. [DOI] [PMID: 9789001]
2.	Ibba, M. and Söll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69 (2000) 617–650. [DOI] [PMID: 10966471]
3.	Raczniak, G., Becker, H.D., Min, B. and Soll, D. A single amidotransferase forms asparaginyl-tRNA and glutaminyl-tRNA in Chlamydia trachomatis. J. Biol. Chem. 276 (2001) 45862–45867. [PMID: 11585842]
4.	Horiuchi, K.Y., Harpel, M.R., Shen, L., Luo, Y., Rogers, K.C. and Copeland, R.A. Mechanistic studies of reaction coupling in Glu-tRNA^Gln amidotransferase. Biochemistry 40 (2001) 6450–6457. [DOI] [PMID: 11371208]
5.	Feng, L., Sheppard, K., Tumbula-Hansen, D. and Soll, D. Gln-tRNA^Gln formation from Glu-tRNA^Gln requires cooperation of an asparaginase and a Glu-tRNA^Gln kinase. J. Biol. Chem. 280 (2005) 8150–8155. [PMID: 15611111]
6.	Nakamura, A., Yao, M., Chimnaronk, S., Sakai, N. and Tanaka, I. Ammonia channel couples glutaminase with transamidase reactions in GatCAB. Science 312 (2006) 1954–1958. [PMID: 16809541]
7.	Wu, J., Bu, W., Sheppard, K., Kitabatake, M., Kwon, S.T., Soll, D. and Smith, J.L. Insights into tRNA-dependent amidotransferase evolution and catalysis from the structure of the Aquifex aeolicus enzyme. J. Mol. Biol. 391 (2009) 703–716. [PMID: 19520089]
8.	Araiso, Y., Huot, J.L., Sekiguchi, T., Frechin, M., Fischer, F., Enkler, L., Senger, B., Ishitani, R., Becker, H.D. and Nureki, O. Crystal structure of Saccharomyces cerevisiae mitochondrial GatFAB reveals a novel subunit assembly in tRNA-dependent amidotransferases. Nucleic Acids Res. 42 (2014) 6052–6063. [PMID: 24692665]

[EC 6.3.5.7 created 2002, modified 2019]

6.3.5.13

Accepted name:

lipid II isoglutaminyl synthase (glutamine-hydrolysing)

Reaction:

ATP + β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol + L-glutamine + H₂O = ADP + phosphate + β-D-GlcNAc-(1→4)-MurNAc-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenol + L-glutamate (overall reaction)
(1a) L-glutamine + H₂O = L-glutamate + NH₃
(1b) ATP + β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol = ADP + β-D-GlcNAc-(1→4)-MurNAc-L-Ala-γ-D-O-P-Glu-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenol
(1c) β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-O-P-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol + NH₃ = β-D-GlcNAc-(1→4)-MurNAc-L-Ala-D-isoglutaminyl-L-Lys-D-Ala-D-Ala-diphospho-ditrans,octacis-undecaprenol + phosphate

Glossary:

lipid II = undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl peptide; the peptide element refers to L-alanyl-D-γ-glutamyl-L-lysyl/meso-2,6-diaminopimelyl-D-alanyl-D-alanine or a modified version thereof = undecaprenyldiphospho-4-O-(N-acetyl-β-D-glucosaminyl)-3-O-peptidyl-α-N-acetylmuramate; the peptide element refers to L-alanyl-D-γ-glutamyl-L-lysyl/meso-2,6-diaminopimelyl-D-alanyl-D-alanine or a modified version thereof

Other name(s):

MurT/GatD; MurT/GatD complex

Systematic name:

β-D-GlcNAc-(1→4)-Mur2Ac(oyl-L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala)-diphospho-ditrans,octacis-undecaprenol:L-glutamine amidoligase (ADP-forming)

Comments:

The enzyme complex, found in Gram-positive bacteria, consists of two subunits. A glutaminase subunit (cf. EC 3.5.1.2, glutaminase) produces an ammonia molecule that is channeled to a ligase subunit, which adds it to the activated D-glutamate residue of lipid II, converting it to an isoglutamine residue.

Links to other databases:

References:

1.	Munch, D., Roemer, T., Lee, S.H., Engeser, M., Sahl, H.G. and Schneider, T. Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus. PLoS Pathog. 8:e1002509 (2012). [PMID: 22291598]
2.	Noldeke, E.R., Muckenfuss, L.M., Niemann, V., Muller, A., Stork, E., Zocher, G., Schneider, T. and Stehle, T. Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus. Sci. Rep. 8:12953 (2018). [PMID: 30154570]
3.	Morlot, C., Straume, D., Peters, K., Hegnar, O.A., Simon, N., Villard, A.M., Contreras-Martel, C., Leisico, F., Breukink, E., Gravier-Pelletier, C., Le Corre, L., Vollmer, W., Pietrancosta, N., Havarstein, L.S. and Zapun, A. Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Nat. Commun. 9:3180 (2018). [PMID: 30093673]

[EC 6.3.5.13 created 2019]

7.2.4.5

Accepted name:

glutaconyl-CoA decarboxylase

Reaction:

(2E)-4-carboxybut-2-enoyl-CoA + Na⁺_{[side 1]} = (2E)-but-2-enoyl-CoA + CO₂ + Na⁺_{[side 2]}

Glossary:

(E)-glutaconyl-CoA = (2E)-4-carboxybut-2-enoyl-CoA

Other name(s):

glutaconyl coenzyme A decarboxylase; pent-2-enoyl-CoA carboxy-lyase; 4-carboxybut-2-enoyl-CoA carboxy-lyase

Systematic name:

(2E)-4-carboxybut-2-enoyl-CoA carboxy-lyase [(2E)-but-2-enoyl-CoA-forming]

Comments:

The enzyme from the bacterium Acidaminococcus fermentans is a biotinyl-protein, requires Na⁺, and acts as a sodium pump. Prior to the Na⁺-dependent decarboxylation, the carboxylate is transferred to biotin in a Na⁺-independent manner. The conserved lysine, to which biotin forms an amide bond, is located 34 amino acids before the C-terminus, flanked on both sides by two methionine residues, which are conserved in every biotin-dependent enzyme.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 84399-93-9

References:

1.	Buckel, W.S. and Semmler, R. Purification, characterisation and reconstitution of glutaconyl-CoA decarboxylase, a biotin-dependent sodium pump from anaerobic bacteria. Eur. J. Biochem. 136 (1983) 427–434. [DOI] [PMID: 6628393]
2.	Buckel, W. Sodium ion-translocating decarboxylases. Biochim. Biophys. Acta 1505 (2001) 15–27. [DOI] [PMID: 11248185]

[EC 7.2.4.5 created 1986 as EC 4.1.1.70, modified 2003, transferred 2019 to EC 7.2.4.5]

7.3.2.7

Accepted name:

arsenite-transporting ATPase

Reaction:

ATP + H₂O + arsenite_{[side 1]} = ADP + phosphate + arsenite_{[side 2]}

Other name(s):

arsAB (gene names)

Systematic name:

ATP phosphohydrolase (arsenite-exporting)

Comments:

This bacterial transporter does not belong to the ABC superfamily, and instead is a member of its own family, referred to as the Ars family. The enzyme usually contains two subunits where one (with 12 membrane-spanning segments) forms the ’channel’ part and the other (occurring in pairs peripherally to the membrane) contains the ATP-binding site. It forms an arsenite efflux pump that removes arsenite from the cytoplasm, and can also remove antimonite anions.

Links to other databases:

References:

1.	Silver, S., Misra, T.K. and Laddaga, R.A. DNA sequence analysis of bacterial toxic heavy metal resistance. Biol. Trace Elem. Res. 21 (1989) 145–163. [PMID: 2484581]
2.	Rosen, B.P., Weigel, U., Monticello, R.A. and Edwards, B.P. Molecular analysis of an anion pump: purification of the ArsC protein. Arch. Biochem. Biophys. 284 (1991) 381–385. [DOI] [PMID: 1703401]
3.	Bruhn, D.F., Li, J., Silver, S., Roberto, F. and Rosen, B.P. The arsenical resistance operon of IncN plasmid R46. FEMS Microbiol. Lett. 139 (1996) 149–153. [PMID: 8674982]
4.	Zhou, T., Rosen, B.P. and Gatti, D.L. Crystallization and preliminary X-ray analysis of the catalytic subunit of the ATP-dependent arsenite pump encoded by the Escherichia coli plasmid R773. Acta Crystallogr. D Biol. Crystallogr. 55 (1999) 921–924. [PMID: 10089335]

[EC 7.3.2.7 created 2000 as EC 3.6.3.16, transferred 2019 to EC 7.3.2.7]

7.4.2.10

Accepted name:

ABC-type glutathione transporter

Reaction:

ATP + H₂O + glutathione-[glutathione-binding protein]_{[side 1]} = ADP + phosphate + glutathione_{[side 2]} + [glutathione-binding protein]_{[side 1]}

Other name(s):

glutathione transporting ATPase; glutathione ABC transporter; gsiACD (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type,glutathione-importing)

Comments:

A prokaryotic ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme from the bacterium Escherichia coli is a heterotrimeric complex that interacts with an extracytoplasmic substrate binding protein to mediate the uptake of glutathione.

Links to other databases:

References:

1.	Suzuki, H., Koyanagi, T., Izuka, S., Onishi, A. and Kumagai, H. The yliA, -B, -C, and -D genes of Escherichia coli K-12 encode a novel glutathione importer with an ATP-binding cassette. J. Bacteriol. 187 (2005) 5861–5867. [PMID: 16109926]
2.	Moussatova, A., Kandt, C., O'Mara, M.L. and Tieleman, D.P. ATP-binding cassette transporters in Escherichia coli. Biochim. Biophys. Acta 1778 (2008) 1757–1771. [PMID: 18634750]

[EC 7.4.2.10 created 2019]

7.4.2.11

Accepted name:

ABC-type methionine transporter

Reaction:

(1) ATP + H₂O + L-methionine-[methionine-binding protein]_{[side 1]} = ADP + phosphate + L-methionine_{[side 2]} + [methionine-binding protein]_{[side 1]}
(2) ATP + H₂O + D-methionine-[methionine-binding protein]_{[side 1]} = ADP + phosphate + D-methionine_{[side 2]} + [methionine-binding protein]_{[side 1]}

Other name(s):

methionine transporting ATPase; methionine ABC transporter; metNIQ (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, methionine-importing)

Comments:

ABC-type (ATP-binding cassette-type) transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. A bacterial enzyme that interacts with an extracytoplasmic substrate binding protein and functions to import methionine. The enzyme from Escherichia coli K-12 mediates the high affinity transport of both L- and D-methionine, as well as methionine-S-oxide and N-acetyl-DL-methionine.

Links to other databases:

References:

1.	Merlin, C., Gardiner, G., Durand, S. and Masters, M. The Escherichia coli metD locus encodes an ABC transporter which includes Abc (MetN), YaeE (MetI), and YaeC (MetQ). J. Bacteriol. 184 (2002) 5513–5517. [PMID: 12218041]
2.	Zhang, Z., Feige, J.N., Chang, A.B., Anderson, I.J., Brodianski, V.M., Vitreschak, A.G., Gelfand, M.S. and Saier, M.H., Jr. A transporter of Escherichia coli specific for L- and D-methionine is the prototype for a new family within the ABC superfamily. Arch. Microbiol. 180 (2003) 88–100. [PMID: 12819857]
3.	Moussatova, A., Kandt, C., O'Mara, M.L. and Tieleman, D.P. ATP-binding cassette transporters in Escherichia coli. Biochim. Biophys. Acta 1778 (2008) 1757–1771. [PMID: 18634750]

[EC 7.4.2.11 created 2019]

7.4.2.12

Accepted name:

ABC-type cystine transporter

Reaction:

(1) ATP + H₂O + L-cystine-[cystine-binding protein]_{[side 1]} = ADP + phosphate + L-cystine_{[side 2]} + [cystine-binding protein]_{[side 1]}
(2) ATP + H₂O + D-cystine-[cystine-binding protein]_{[side 1]} = ADP + phosphate + D-cystine_{[side 2]} + [cystine-binding protein]_{[side 1]}

Other name(s):

cystine transporting ATPase; cystine ABC transporter

Systematic name:

ATP phosphohydrolase (ABC-type, cystine-importing)

Comments:

ABC-type (ATP-binding cassette-type) transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. A bacterial enzyme that interacts with an extracytoplasmic substrate binding protein and mediates the high affinity import of trace cystine. The enzyme from Escherichia coli K-12 can import both isomers of cystine and a variety of related molecules including djenkolate, lanthionine, diaminopimelate and homocystine.

Links to other databases:

References:

1.	Berger, E.A. and Heppel, L.A. A binding protein involved in the transport of cystine and diaminopimelic acid in Escherichia coli. J. Biol. Chem. 247 (1972) 7684–7694. [PMID: 4564569]
2.	Chonoles Imlay, K.R., Korshunov, S. and Imlay, J.A. Physiological roles and adverse effects of the two cystine importers of Escherichia coli. J. Bacteriol. 197 (2015) 3629–3644. [PMID: 26350134]

[EC 7.4.2.12 created 2019]

7.5.2.7

Accepted name:

ABC-type D-ribose transporter

Reaction:

ATP + H₂O + D-ribose-[ribose-binding protein]_{[side 1]} = ADP + phosphate + D-ribose_{[side 2]} + [ribose-binding protein]_{[side 1]}

Other name(s):

D-ribose transporting ATPase; D-ribose ABC transporter; rbsACB (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, D-ribose-importing)

Comments:

ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. A bacterial enzyme that interacts with an extracytoplasmic substrate binding protein and mediates the high affinity uptake of D-ribose.

Links to other databases:

References:

1.	Bell, A.W., Buckel, S.D., Groarke, J.M., Hope, J.N., Kingsley, D.H. and Hermodson, M.A. The nucleotide sequences of the rbsD, rbsA, and rbsC genes of Escherichia coli K12. J. Biol. Chem. 261 (1986) 7652–7658. [PMID: 3011793]
2.	Clifton, M.C., Simon, M.J., Erramilli, S.K., Zhang, H., Zaitseva, J., Hermodson, M.A. and Stauffacher, C.V. In vitro reassembly of the ribose ATP-binding cassette transporter reveals a distinct set of transport complexes. J. Biol. Chem. 290 (2015) 5555–5565. [PMID: 25533465]

[EC 7.5.2.7 created 2019]

7.5.2.8

Accepted name:

ABC-type D-allose transporter

Reaction:

ATP + H₂O + D-allose-[allose-binding protein]_{[side 1]} = ADP + phosphate + D-allose_{[side 2]} + [allose-binding protein]_{[side 1]}

Other name(s):

D-allose transporting ATPase; D-allose ABC transporter; alsBAC (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, D-allose-importing)

Comments:

ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme from the bacterium Escherichia coli interacts with an extracytoplasmic substrate binding protein and mediates the high affinity uptake of D-allose, which can be used by the bacterium as a sole carbon source.

Links to other databases:

References:

1.	Kim, C., Song, S. and Park, C. The D-allose operon of Escherichia coli K-12. J. Bacteriol. 179 (1997) 7631–7637. [PMID: 9401019]

[EC 7.5.2.8 created 2019]

7.5.2.9

Accepted name:

ABC-type D-galactofuranose transporter

Reaction:

ATP + H₂O + D-galactofuranose-[galactofuranose-binding protein]_{[side 1]} = ADP + phosphate + D-galactofuranose_{[side 2]} + [galactofuranose-binding protein]_{[side 1]}

Other name(s):

D-galactofuranose transporting ATPase; D-galactofuranose ABC transporter

Systematic name:

ATP phosphohydrolase (ABC-type, D-galactofuranose-transporting)

Comments:

ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. The enzyme from Escherichai coli interacts with a periplasmic substrate binding protein and mediates the high affinity uptake of D-galactofuranose. The periplasmic binding protein exhibits selective binding of D-galactofuranose over D-galactopyranose.

Links to other databases:

References:

1.	Horler, R.S., Muller, A., Williamson, D.C., Potts, J.R., Wilson, K.S. and Thomas, G.H. Furanose-specific sugar transport: characterization of a bacterial galactofuranose-binding protein. J. Biol. Chem. 284 (2009) 31156–31163. [PMID: 19744923]

[EC 7.5.2.9 created 2019]

7.5.2.10

Accepted name:

ABC-type D-xylose transporter

Reaction:

ATP + H₂O + D-xylose-[xylose-binding protein]_{[side 1]} = ADP + phosphate + D-xylose_{[side 2]} + [xylose-binding protein]_{[side 1]}

Other name(s):

D-xylose transporting ATPase; D-xylose ABC transporter; xylFGH (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, D-xylose-transporting)

Comments:

Links to other databases:

References:

1.	Song, S. and Park, C. Organization and regulation of the D-xylose operons in Escherichia coli K-12: XylR acts as a transcriptional activator. J. Bacteriol. 179 (1997) 7025–7032. [PMID: 9371449]
2.	Linton, K.J. and Higgins, C.F. The Escherichia coli ATP-binding cassette (ABC) proteins. Mol. Microbiol. 28 (1998) 5–13. [PMID: 9593292]

[EC 7.5.2.10 created 2019]

7.5.2.11

Accepted name:

ABC-type D-galactose transporter

Reaction:

ATP + H₂O + D-galactose-[galactose-binding protein]_{[side 1]} = ADP + phosphate + D-galactose_{[side 2]} + [galactose-binding protein]_{[side 1]}

Other name(s):

D-galactose transporting ATPase; D-galactose ABC transporter; mglBAC (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, D-galactose-importing)

Comments:

ATP-binding cassette (ABC) type transporter, characterized by the presence of two similar ATP-binding domains/proteins and two integral membrane domains/proteins. A bacterial enzyme, best characterized from Escherichia coli where it interacts with a periplasmic substrate binding protein and mediates the high affinity uptake of D-galactose and methyl-β-D-galactoside.

Links to other databases:

References:

1.	Hogg, R.W., Voelker, C. and Von Carlowitz, I. Nucleotide sequence and analysis of the mgl operon of Escherichia coli K12. Mol. Gen. Genet. 229 (1991) 453–459. [PMID: 1719366]

[EC 7.5.2.11 created 2019]

7.5.2.12

Accepted name:

ABC-type L-arabinose transporter

Reaction:

ATP + H₂O + L-arabinose-[arabinose-binding protein]_{[side 1]} = ADP + phosphate + L-arabinose_{[side 2]} + [arabinose-binding protein]_{[side 1]}

Other name(s):

L-arabinose transporting ATPase; L-arabinose ABC transporter; araFGH (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, L-arabinose-importing)

Comments:

Links to other databases:

References:

1.	Scripture, J.B., Voelker, C., Miller, S., O'Donnell, R.T., Polgar, L., Rade, J., Horazdovsky, B.F. and Hogg, R.W. High-affinity L-arabinose transport operon. Nucleotide sequence and analysis of gene products. J. Mol. Biol. 197 (1987) 37–46. [PMID: 2445996]
2.	Horazdovsky, B.F. and Hogg, R.W. Genetic reconstitution of the high-affinity L-arabinose transport system. J. Bacteriol. 171 (1989) 3053–3059. [PMID: 2656640]

[EC 7.5.2.12 created 2019]

7.5.2.13

Accepted name:

ABC-type D-xylose/L-arabinose transporter

Reaction:

(1) ATP + H₂O + D-xylose-[xylose-binding protein]_{[side 1]} = ADP + phosphate + D-xylose_{[side 2]} + [xylose-binding protein]_{[side 1]}
(2) ATP + H₂O + L-arabinose-[arabinose-binding protein]_{[side 1]} = ADP + phosphate + L-arabinose_{[side 2]} + [arabinose-binding protein]_{[side 1]}

Systematic name:

ATP phosphohydrolase (ABC-type, D-xylose/L-arabinose-importing)

Comments:

ATP-binding cassette (ABC) type transporter with a 10-transmembrane-spanning (TMD) subunit and a single nucleotide binding domain. The enzyme from the archaeon Sulfolobus acidocaldarius interacts with an extracytoplasmic sugar-binding protein and mediates the uptake of of D-xylose and L-arabinose (cf. EC 7.5.2.10, ABC-type D-xylose transporter and EC 7.5.2.12, ABC-type L-arabinose transporter).

Links to other databases:

References:

Wagner, M., Shen, L., Albersmeier, A., van der Kolk, N., Kim, S., Cha, J., Braesen, C., Kalinowski, J., Siebers, B. and Albers, S.-V. Sulfolobus acidocaldarius transports pentoses via a carbohydrate uptake transporter 2 (CUT2)-type ABC transporter and metabolizes them through the aldolase-independent Weimberg pathway. Appl. Environ. Microbiol. 84 (2018) e01273–17. [PMID: 29150511]

[EC 7.5.2.13 created 2019]

7.6.2.13

Accepted name:

ABC-type autoinducer-2 transporter

Reaction:

ATP + H₂O + (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran-[AI-2-binding protein]_{[side 1]} = ADP + phosphate + (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran_{[side 2]} + [AI-2-binding protein]_{[side 1]}

Glossary:

autoinducer-2 = AI-2 = (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran

Other name(s):

autoinducer-2 transporting ATPase; autoinducer-2 ABC transporter; LsrACDB (gene names)

Systematic name:

ATP phosphohydrolase (ABC-type, AI-2 importing)

Comments:

Links to other databases: