The Enzyme Database

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

Proposed Changes to the Enzyme List

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 To prevent confusion please do not quote new EC numbers until they are incorporated into the main list.

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

Contents

*EC 1.2.1.25 branched-chain α-keto acid dehydrogenase system
EC 1.2.1.104 pyruvate dehydrogenase system
EC 1.2.1.105 2-oxoglutarate dehydrogenase system
*EC 1.3.8.5 short-chain 2-methylacyl-CoA dehydrogenase
EC 1.3.8.16 2-amino-4-deoxychorismate dehydrogenase
EC 1.3.99.12 transferred
EC 1.3.99.24 transferred
EC 1.4.1.27 glycine cleavage system
EC 1.4.3.26 pre-mycofactocin synthase
EC 1.13.11.91 3-mercaptopropionate dioxygenase
EC 1.14.11.76 L-glutamate 3(R)-hydroxylase
*EC 1.14.14.139 5β-cholestane-3α,7α-diol 12α-hydroxylase
EC 1.14.15.38 N,N-dimethyl phenylurea N-demethylase
EC 1.14.18.8 transferred
*EC 1.14.99.38 cholesterol 25-monooxygenase
EC 1.14.99.67 α-N-dichloroacetyl-p-aminophenylserinol N-oxygenase
EC 1.14.99.68 4-aminobenzoate N-oxygenase
EC 1.14.99.69 tRNA 2-(methylsulfanyl)-N6-isopentenyladenosine37 hydroxylase
EC 1.17.98.4 formate dehydrogenase (hydrogenase)
EC 1.17.99.7 transferred
EC 1.17.99.9 heme a synthase
EC 1.17.99.10 steroid C-25 hydroxylase
EC 1.17.99.11 3-oxo-Δ1-steroid hydratase/dehydrogenase
EC 2.1.1.373 2-hydroxy-4-(methylsulfanyl)butanoate S-methyltransferase
EC 2.1.1.374 2-heptyl-1-hydroxyquinolin-4(1H)-one methyltransferase
EC 2.2.1.13 apulose-4-phosphate transketolase
*EC 2.3.1.179 β-ketoacyl-[acyl-carrier-protein] synthase II
*EC 2.3.1.190 acetoin dehydrogenase system
EC 2.3.2.36 RING-type E3 ubiquitin transferase (cysteine targeting)
*EC 2.4.2.29 tRNA-guanosine34 preQ1 transglycosylase
EC 2.4.2.64 tRNA-guanosine34 queuine transglycosylase
*EC 2.5.1.25 tRNA-uridine aminocarboxypropyltransferase
EC 2.5.1.153 adenosine tuberculosinyltransferase
*EC 2.7.7.69 GDP-L-galactose/GDP-D-glucose: hexose 1-phosphate guanylyltransferase
*EC 2.7.7.88 GDP polyribonucleotidyltransferase
EC 3.1.1.115 D-apionolactonase
EC 3.1.3.31 deleted
EC 3.1.7.8 transferred
EC 3.1.7.9 transferred
EC 3.5.1.136 N,N′-diacetylchitobiose non-reducing end deacetylase
EC 3.7.1.27 neryl diphosphate diphosphatase
EC 5.1.3.44 mannose 2-epimerase
EC 5.3.1.36 D-apiose isomerase

*EC 1.2.1.25
Accepted name: branched-chain α-keto acid dehydrogenase system
Reaction: 3-methyl-2-oxobutanoate + CoA + NAD+ = 2-methylpropanoyl-CoA + CO2 + NADH
Other name(s): branched-chain α-keto acid dehydrogenase complex; 2-oxoisovalerate dehydrogenase; α-ketoisovalerate dehydrogenase; 2-oxoisovalerate dehydrogenase (acylating)
Systematic name: 3-methyl-2-oxobutanoate:NAD+ 2-oxidoreductase (CoA-methylpropanoylating)
Comments: This enzyme system catalyses the oxidative decarboxylation of branched-chain α-keto acids derived from L-leucine, L-isoleucine, and L-valine to branched-chain acyl-CoAs. It belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.104, pyruvate dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.4, 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring), EC 2.3.1.168, dihydrolipoyllysine-residue (2-methylpropanoyl)transferase, and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The system also acts on (S)-3-methyl-2-oxopentanoate and 4-methyl-2-oxopentanoate.
Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 37211-61-3
References:
1.  Namba, Y., Yoshizawa, K., Ejima, A., Hayashi, T. and Kaneda, T. Coenzyme A- and nicotinamide adenine dinucleotide-dependent branched chain α-keto acid dehydrogenase. I. Purification and properties of the enzyme from Bacillus subtilis. J. Biol. Chem. 244 (1969) 4437–4447. [PMID: 4308861]
2.  Pettit, F.H., Yeaman, S.J. and Reed, L.J. Purification and characterization of branched chain α-keto acid dehydrogenase complex of bovine kidney. Proc. Natl. Acad. Sci. USA 75 (1978) 4881–4885. [DOI] [PMID: 283398]
3.  Harris, R.A., Hawes, J.W., Popov, K.M., Zhao, Y., Shimomura, Y., Sato, J., Jaskiewicz, J. and Hurley, T.D. Studies on the regulation of the mitochondrial α-ketoacid dehydrogenase complexes and their kinases. Adv. Enzyme Regul. 37 (1997) 271–293. [DOI] [PMID: 9381974]
4.  Evarsson, A., Chuang, J.L., Wynn, R.M., Turley, S., Chuang, D.T. and Hol, W.G. Crystal structure of human branched-chain α-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease. Structure 8 (2000) 277–291. [PMID: 10745006]
5.  Reed, L.J. A trail of research from lipoic acid to α-keto acid dehydrogenase complexes. J. Biol. Chem. 276 (2001) 38329–38336. [DOI] [PMID: 11477096]
[EC 1.2.1.25 created 1972, modified 2019, modified 2020]
 
 
EC 1.2.1.104
Accepted name: pyruvate dehydrogenase system
Reaction: pyruvate + CoA + NAD+ = acetyl-CoA + CO2 + NADH
Other name(s): pyruvate dehydrogenase complex; PDH
Systematic name: pyruvate:NAD+ 2-oxidoreductase (CoA-acetylating)
Comments: The pyruvate dehydrogenase system (PDH) is a large enzyme complex that belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.25, branched-chain α-keto acid dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and a dihydrolipoamide dehydrogenase (E3). The reaction catalysed by this system is the sum of three activities: EC 1.2.4.1, pyruvate dehydrogenase (acetyl-transferring) (E1), EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase (E2), and EC 1.8.1.4, dihydrolipoyl dehydrogenase (E3). The mammalian system also includes E3 binding protein, which is involved in the interaction between the E2 and E3 subunits.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Reed, L.J., Pettit, F.H., Eley, M.H., Hamilton, L., Collins, J.H. and Oliver, R.M. Reconstitution of the Escherichia coli pyruvate dehydrogenase complex. Proc. Natl. Acad. Sci. USA 72 (1975) 3068–3072. [DOI] [PMID: 1103138]
2.  Bates, D.L., Danson, M.J., Hale, G., Hooper, E.A. and Perham, R.N. Self-assembly and catalytic activity of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. Nature 268 (1977) 313–316. [DOI] [PMID: 329143]
3.  Stanley, C.J., Packman, L.C., Danson, M.J., Henderson, C.E. and Perham, R.N. Intramolecular coupling of active sites in the pyruvate dehydrogenase multienzyme complexes from bacterial and mammalian sources. Biochem. J. 195 (1981) 715–721. [DOI] [PMID: 7032507]
4.  Yang, H.C., Hainfeld, J.F., Wall, J.S. and Frey, P.A. Quaternary structure of pyruvate dehydrogenase complex from Escherichia coli. J. Biol. Chem. 260 (1985) 16049–16051. [PMID: 3905803]
5.  Patel, M.S. and Roche, T.E. Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J. 4 (1990) 3224–3233. [DOI] [PMID: 2227213]
[EC 1.2.1.104 created 2020]
 
 
EC 1.2.1.105
Accepted name: 2-oxoglutarate dehydrogenase system
Reaction: 2-oxoglutarate + CoA + NAD+ = succinyl-CoA + CO2 + NADH
Other name(s): 2-oxoglutarate dehydrogenase complex
Systematic name: 2-oxoglutarate:NAD+ 2-oxidoreductase (CoA-succinylating)
Comments: The 2-oxoglutarate dehydrogenase system is a large enzyme complex that belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.25, branched-chain α-keto acid dehydrogenase system, EC 1.2.1.104, pyruvate dehydrogenase system, EC 1.4.1.27, glycine cleavage system, and EC 2.3.1.190, acetoin dehydrogenase system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and a dihydrolipoamide dehydrogenase (E3). This enzyme system converts 2-oxoglutarate to succinyl-CoA and produces NADH and CO2 in a complicated series of irreversible reactions. The reaction catalysed by this system is the sum of three activities: EC 1.2.4.2, oxoglutarate dehydrogenase (succinyl-transferring) (E1), EC 2.3.1.61, dihydrolipoyllysine-residue succinyltransferase (E2) and EC 1.8.1.4, dihydrolipoyl dehydrogenase (E3).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Robien, M.A., Clore, G.M., Omichinski, J.G., Perham, R.N., Appella, E., Sakaguchi, K. and Gronenborn, A.M. Three-dimensional solution structure of the E3-binding domain of the dihydrolipoamide succinyltransferase core from the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli. Biochemistry 31 (1992) 3463–3471. [DOI] [PMID: 1554728]
2.  Knapp, J.E., Mitchell, D.T., Yazdi, M.A., Ernst, S.R., Reed, L.J. and Hackert, M.L. Crystal structure of the truncated cubic core component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex. J. Mol. Biol. 280 (1998) 655–668. [DOI] [PMID: 9677295]
3.  Reed, L.J. A trail of research from lipoic acid to α-keto acid dehydrogenase complexes. J. Biol. Chem. 276 (2001) 38329–38336. [DOI] [PMID: 11477096]
4.  Murphy, G.E. and Jensen, G.J. Electron cryotomography of the E. coli pyruvate and 2-oxoglutarate dehydrogenase complexes. Structure 13 (2005) 1765–1773. [DOI] [PMID: 16338405]
5.  Frank, R.A., Price, A.J., Northrop, F.D., Perham, R.N. and Luisi, B.F. Crystal structure of the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex. J. Mol. Biol. 368 (2007) 639–651. [DOI] [PMID: 17367808]
6.  Bunik, V.I. and Degtyarev, D. Structure-function relationships in the 2-oxo acid dehydrogenase family: substrate-specific signatures and functional predictions for the 2-oxoglutarate dehydrogenase-like proteins. Proteins 71 (2008) 874–890. [DOI] [PMID: 18004749]
7.  Shim da, J., Nemeria, N.S., Balakrishnan, A., Patel, H., Song, J., Wang, J., Jordan, F. and Farinas, E.T. Assignment of function to histidines 260 and 298 by engineering the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase complex; substitutions that lead to acceptance of substrates lacking the 5-carboxyl group. Biochemistry 50 (2011) 7705–7709. [DOI] [PMID: 21809826]
[EC 1.2.1.105 created 2020]
 
 
*EC 1.3.8.5
Accepted name: short-chain 2-methylacyl-CoA dehydrogenase
Reaction: 2-methylbutanoyl-CoA + electron-transfer flavoprotein = (E)-2-methylbut-2-enoyl-CoA + reduced electron-transfer flavoprotein + H+
Other name(s): ACADSB (gene name); 2-methylacyl-CoA dehydrogenase; branched-chain acyl-CoA dehydrogenase (ambiguous); 2-methyl branched chain acyl-CoA dehydrogenase; 2-methylbutanoyl-CoA:(acceptor) oxidoreductase; 2-methyl-branched-chain-acyl-CoA:electron-transfer flavoprotein 2-oxidoreductase; 2-methyl-branched-chain-enoyl-CoA reductase
Systematic name: short-chain 2-methylacyl-CoA:electron-transfer flavoprotein 2-oxidoreductase
Comments: A flavoprotein (FAD). The mammalian enzyme catalyses an oxidative reaction as a step in the mitochondrial β-oxidation of short-chain 2-methyl fatty acids and participates in isoleucine degradation. The enzyme from the parasitic helminth Ascaris suum catalyses a reductive reaction as part of a fermentation pathway, shuttling reducing power from the electron-transport chain to 2-methyl branched-chain enoyl CoA.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Ikeda, Y., Dabrowski, C. and Tanaka, K. Separation and properties of five distinct acyl-CoA dehydrogenases from rat liver mitochondria. Identification of a new 2-methyl branched chain acyl-CoA dehydrogenase. J. Biol. Chem. 258 (1983) 1066–1076. [PMID: 6401712]
2.  Komuniecki, R., Fekete, S. and Thissen-Parra, J. Purification and characterization of the 2-methyl branched-chain acyl-CoA dehydrogenase, an enzyme involved in NADH-dependent enoyl-CoA reduction in anaerobic mitochondria of the nematode, Ascaris suum. J. Biol. Chem. 260 (1985) 4770–4777. [PMID: 3988734]
3.  Komuniecki, R., McCrury, J., Thissen, J. and Rubin, N. Electron-transfer flavoprotein from anaerobic Ascaris suum mitochondria and its role in NADH-dependent 2-methyl branched-chain enoyl-CoA reduction. Biochim. Biophys. Acta 975 (1989) 127–131. [DOI] [PMID: 2736251]
4.  Vockley, J., Mohsen al,-W., A., Binzak, B., Willard, J. and Fauq, A. Mammalian branched-chain acyl-CoA dehydrogenases: molecular cloning and characterization of recombinant enzymes. Methods Enzymol. 324 (2000) 241–258. [DOI] [PMID: 10989435]
5.  Andresen, B.S., Christensen, E., Corydon, T.J., Bross, P., Pilgaard, B., Wanders, R.J., Ruiter, J.P., Simonsen, H., Winter, V., Knudsen, I., Schroeder, L.D., Gregersen, N. and Skovby, F. Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. Am. J. Hum. Genet. 67 (2000) 1095–1103. [DOI] [PMID: 11013134]
[EC 1.3.8.5 created 1992 as EC 1.3.1.52, transferred 2012 to EC 1.3.8.5 (EC 1.3.99.12, created 1986, incorporated 2020), modified 2020]
 
 
EC 1.3.8.16
Accepted name: 2-amino-4-deoxychorismate dehydrogenase
Reaction: (2S)-2-amino-4-deoxychorismate + FMN = 3-(1-carboxyvinyloxy)anthranilate + FMNH2
For diagram of enediyne antitumour antibiotic biosynthesis, click here
Glossary: (2S)-2-amino-4-deoxychorismate = (2S,3S)-3-(1-carboxyvinyloxy)-2,3-dihydroanthranilate
3-enolpyruvoylanthranilate = 3-(1-carboxyvinyloxy)anthranilate
Other name(s): ADIC dehydrogenase; 2-amino-2-deoxyisochorismate dehydrogenase; SgcG
Systematic name: (2S)-2-amino-4-deoxychorismate:FMN oxidoreductase
Comments: The sequential action of EC 2.6.1.86, 2-amino-4-deoxychorismate synthase and this enzyme leads to the formation of the benzoxazolinate moiety of the enediyne antitumour antibiotic C-1027 [1,2].
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Van Lanen, S.G., Lin, S. and Shen, B. Biosynthesis of the enediyne antitumor antibiotic C-1027 involves a new branching point in chorismate metabolism. Proc. Natl. Acad. Sci. USA 105 (2008) 494–499. [DOI] [PMID: 18182490]
2.  Yu, L., Mah, S., Otani, T. and Dedon, P. The benzoxazolinate of C-1027 confers intercalative DNA binding. J. Am. Chem. Soc. 117 (1995) 8877–8878. [DOI]
[EC 1.3.8.16 created 2008 as 1.3.99.24, transferred 2020 to EC 1.3.8.16.]
 
 
EC 1.3.99.12
Transferred entry: 2-methylacyl-CoA dehydrogenase. Now classified as EC 1.3.8.5, 2-methyl-branched-chain-enoyl-CoA reductase.
[EC 1.3.99.12 created 1986, deleted 2020]
 
 
EC 1.3.99.24
Transferred entry: 2-amino-4-deoxychorismate dehydrogenase. Now EC 1.3.8.16, 2-amino-4-deoxychorismate dehydrogenase
[EC 1.3.99.24 created 2008, deleted 2020]
 
 
EC 1.4.1.27
Accepted name: glycine cleavage system
Reaction: glycine + tetrahydrofolate + NAD+ = 5,10-methylenetetrahydrofolate + NH3 + CO2 + NADH
Other name(s): GCV
Systematic name: glycine:NAD+ 2-oxidoreductase (tetrahydrofolate-methylene-adding)
Comments: The glycine cleavage (GCV) system is a large multienzyme complex that belongs to the 2-oxoacid dehydrogenase complex family, which also includes EC 1.2.1.25, branched-chain α-keto acid dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.2.1.104, pyruvate dehydrogenase system, and EC 2.3.1.190, acetoin dehydrogenase system. The GCV system catalyses the reversible oxidation of glycine, yielding carbon dioxide, ammonia, 5,10-methylenetetrahydrofolate and a reduced pyridine nucleotide. Tetrahydrofolate serves as a recipient for one-carbon units generated during glycine cleavage to form the methylene group. The GCV system consists of four protein components, the P protein (EC 1.4.4.2, glycine dehydrogenase (aminomethyl-transferring)), T protein (EC 2.1.2.10, aminomethyltransferase), L protein (EC 1.8.1.4, dihydrolipoyl dehydrogenase), and the non-enzyme H protein (lipoyl-carrier protein). The P protein catalyses the pyridoxal phosphate-dependent liberation of CO2 from glycine, leaving a methylamine moiety. The methylamine moiety is transferred to the lipoic acid group of the H protein, which is bound to the P protein prior to decarboxylation of glycine. The T protein catalyses the release of ammonia from the methylamine group and transfers the remaining C1 unit to tetrahydrofolate, forming 5,10-methylenetetrahydrofolate. The L protein then oxidizes the lipoic acid component of the H protein and transfers the electrons to NAD+, forming NADH.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Motokawa, Y. and Kikuchi, G. Glycine metabolism by rat liver mitochondria. Reconstruction of the reversible glycine cleavage system with partially purified protein components. Arch. Biochem. Biophys. 164 (1974) 624–633. [DOI] [PMID: 4460882]
2.  Hiraga, K. and Kikuchi, G. The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein. J. Biol. Chem. 255 (1980) 11671–11676. [PMID: 7440563]
3.  Okamura-Ikeda, K., Fujiwara, K. and Motokawa, Y. Purification and characterization of chicken liver T-protein, a component of the glycine cleavage system. J. Biol. Chem. 257 (1982) 135–139. [PMID: 7053363]
4.  Fujiwara, K., Okamura-Ikeda, K. and Motokawa, Y. Mechanism of the glycine cleavage reaction. Further characterization of the intermediate attached to H-protein and of the reaction catalyzed by T-protein. J. Biol. Chem. 259 (1984) 10664–10668. [PMID: 6469978]
5.  Okamura-Ikeda, K., Ohmura, Y., Fujiwara, K. and Motokawa, Y. Cloning and nucleotide sequence of the gcv operon encoding the Escherichia coli glycine-cleavage system. Eur. J. Biochem. 216 (1993) 539–548. [DOI] [PMID: 8375392]
[EC 1.4.1.27 created 2020]
 
 
EC 1.4.3.26
Accepted name: pre-mycofactocin synthase
Reaction: 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + O2 + H2O = 5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidine-2,3-dione + NH3 + H2O2 (overall reaction)
(1a) 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + O2 = 5-[(4-hydroxyphenyl)methyl]-3-imino-4,4-dimethylpyrrolidin-2-one + H2O2
(1b) 5-[(4-hydroxyphenyl)methyl]-3-imino-4,4-dimethylpyrrolidin-2-one + H2O = 5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidine-2,3-dione + NH3 (spontaneous)
Glossary: 5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidine-2,3-dione = pre-mycofactocinone = PMFT
Other name(s): mftD (gene name)
Systematic name: 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one:oxygen oxidoreductase
Comments: A flavoprotein (FMN). The enzyme participates in the biosynthesis of the enzyme cofactor mycofactocin. The enzyme uses oxygen as an electron source to oxidize a C-N bond, followed by spontaneous exchange with water to form an α-keto moiety on the resulting molecule.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Ayikpoe, R.S. and Latham, J.A. MftD catalyzes the formation of a biologically active redox center in the biosynthesis of the ribosomally synthesized and post-translationally modified redox cofactor mycofactocin. J. Am. Chem. Soc. 141 (2019) 13582–13591. [DOI] [PMID: 31381312]
[EC 1.4.3.26 created 2020]
 
 
EC 1.13.11.91
Accepted name: 3-mercaptopropionate dioxygenase
Reaction: 3-sulfanylpropanoate + O2 = 3-sulfinopropanoate
Other name(s): mdo (gene name); 3-mercaptopropionic acid dioxygenase; 3-sulfanylpropanoate dioxygenase
Systematic name: 3-sulfanylpropanoate:oxygen oxidoreductase
Comments: This bacterial enzyme contains an iron(2+) atom coordinated by three protein-derived histidines and a Ser-His-Tyr motif. It is similar to EC 1.13.11.20, cysteine dioxygenase, and can act on L-cysteine, but has a much higher activity with its native substrate, 3-sulfanylpropanoate.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Bruland, N., Wubbeler, J.H. and Steinbuchel, A. 3-Mercaptopropionate dioxygenase, a cysteine dioxygenase homologue, catalyzes the initial step of 3-mercaptopropionate catabolism in the 3,3-thiodipropionic acid-degrading bacterium Variovorax paradoxus. J. Biol. Chem. 284 (2009) 660–672. [DOI] [PMID: 19001372]
2.  Driggers, C.M., Hartman, S.J. and Karplus, P.A. Structures of Arg- and Gln-type bacterial cysteine dioxygenase homologs. Protein Sci. 24 (2015) 154–161. [DOI] [PMID: 25307852]
3.  Pierce, B.S., Subedi, B.P., Sardar, S. and Crowell, J.K. The ’Gln-type’ thiol dioxygenase from Azotobacter vinelandii is a 3-mercaptopropionic acid dioxygenase. Biochemistry 54 (2015) 7477–7490. [DOI] [PMID: 26624219]
4.  Tchesnokov, E.P., Fellner, M., Siakkou, E., Kleffmann, T., Martin, L.W., Aloi, S., Lamont, I.L., Wilbanks, S.M. and Jameson, G.N. The cysteine dioxygenase homologue from Pseudomonas aeruginosa is a 3-mercaptopropionate dioxygenase. J. Biol. Chem. 290 (2015) 24424–24437. [DOI] [PMID: 26272617]
5.  Fellner, M., Aloi, S., Tchesnokov, E.P., Wilbanks, S.M. and Jameson, G.N. Substrate and pH-dependent kinetic profile of 3-mercaptopropionate dioxygenase from Pseudomonas aeruginosa. Biochemistry 55 (2016) 1362–1371. [DOI] [PMID: 26878277]
6.  Crowell, J.K., Sardar, S., Hossain, M.S., Foss, F.W., Jr. and Pierce, B.S. Non-chemical proton-dependent steps prior to O2-activation limit Azotobacter vinelandii 3-mercaptopropionic acid dioxygenase (MDO) catalysis. Arch. Biochem. Biophys. 604 (2016) 86–94. [DOI] [PMID: 27311613]
7.  Aloi, S., Davies, C.G., Karplus, P.A., Wilbanks, S.M. and Jameson, G.NL. Substrate specificity in thiol dioxygenases. Biochemistry 58 (2019) 2398–2407. [DOI] [PMID: 31045343]
8.  Sardar, S., Weitz, A., Hendrich, M.P. and Pierce, B.S. Outer-sphere tyrosine 159 within the 3-mercaptopropionic acid dioxygenase S-H-Y motif gates substrate-coordination denticity at the non-heme iron active site. Biochemistry 58 (2019) 5135–5150. [DOI] [PMID: 31750652]
[EC 1.13.11.91 created 2020]
 
 
EC 1.14.11.76
Accepted name: L-glutamate 3(R)-hydroxylase
Reaction: L-glutamate + 2-oxoglutarate + O2 = (3R)-3-hydroxy-L-glutamate + succinate + CO2
Glossary: ibotenate = (S)-2-amino-2-(3-hydroxyisoxazol-5-yl)acetate
muscimol = 5-(aminomethyl)-1,2-oxazol-3-ol
Other name(s): iboH (gene name)
Systematic name: L-glutamate,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)
Comments: Requires Fe2+ and L-ascorbate. The enzyme, characterized from the basidiomycete mushroom Amanita muscaria, participates in the biosynthesis of the psychoactive compounds ibotenate and muscimol.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Obermaier, S. and Muller, M. Ibotenic acid biosynthesis in the fly agaric is initiated by glutamate hydroxylation. Angew. Chem. Int. Ed. Engl. 59 (2020) 12432–12435. [DOI] [PMID: 32233056]
[EC 1.14.11.76 created 2020]
 
 
*EC 1.14.14.139
Accepted name: 5β-cholestane-3α,7α-diol 12α-hydroxylase
Reaction: (1) 5β-cholestane-3α,7α-diol + [reduced NADPH—hemoprotein reductase] + O2 = 5β-cholestane-3α,7α,12α-triol + [oxidized NADPH—hemoprotein reductase] + H2O
(2) 7α-hydroxycholest-4-en-3-one + [reduced NADPH—hemoprotein reductase] + O2 = 7α,12α-dihydroxycholest-4-en-3-one + [oxidized NADPH—hemoprotein reductase] + H2O
(3) chenodeoxycholate + [reduced NADPH—hemoprotein reductase] + O2 = cholate + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of cholesterol catabolism (rings A, B and C), click here
Glossary: chenodeoxycholate = 3α,7α-dihydroxy-5β-cholan-24-oate
cholate = 3α,7α-12α-trihydroxy-5β-cholan-24-oate
Other name(s): 5β-cholestane-3α,7α-diol 12α-monooxygenase; sterol 12α-hydroxylase (ambiguous); CYP8B1; cytochrome P450 8B1; 7α-hydroxycholest-4-en-3-one 12α-hydroxylase; 7α-hydroxy-4-cholesten-3-one 12α-monooxygenase; chenodeoxycholate 12α monooxygenase
Systematic name: 5β-cholestane-3α,7α-diol,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (12α-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein found in mammals. This is the key enzyme in the biosynthesis of the bile acid cholate. The enzyme can also hydroxylate 5β-cholestane-3α,7α-diol at the 25 and 26 position, but to a lesser extent [2].
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis and metabolism of bile acids. Catalytic properties of different forms of cytochrome P-450. J. Biol. Chem. 255 (1980) 1643–1649. [PMID: 6766451]
2.  Hansson, R. and Wikvall, K. Hydroxylations in biosynthesis of bile acids. Cytochrome P-450 LM4 and 12α-hydroxylation of 5β-cholestane-3α,7α-diol. Eur. J. Biochem. 125 (1982) 423–429. [DOI] [PMID: 6811268]
3.  Ishida, H., Noshiro, M., Okuda, K. and Coon, M.J. Purification and characterization of 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase. J. Biol. Chem. 267 (1992) 21319–21323. [PMID: 1400444]
4.  Eggertsen, G., Olin, M., Andersson, U., Ishida, H., Kubota, S., Hellman, U., Okuda, K.I. and Björkhem, I. Molecular cloning and expression of rabbit sterol 12α-hydroxylase. J. Biol. Chem. 271 (1996) 32269–32275. [DOI] [PMID: 8943286]
5.  Lundell, K. and Wikvall, K. Gene structure of pig sterol 12α-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6α-hydroxylase (CYP4A21). Biochim. Biophys. Acta 1634 (2003) 86–96. [DOI] [PMID: 14643796]
6.  del Castillo-Olivares, A. and Gil, G. α1-Fetoprotein transcription factor is required for the expression of sterol 12α -hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription. J. Biol. Chem. 275 (2000) 17793–17799. [DOI] [PMID: 10747975]
7.  Yang, Y., Zhang, M., Eggertsen, G. and Chiang, J.Y. On the mechanism of bile acid inhibition of rat sterol 12α-hydroxylase gene (CYP8B1) transcription: roles of α-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha. Biochim. Biophys. Acta 1583 (2002) 63–73. [DOI] [PMID: 12069850]
8.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
9.  Fan, L., Joseph, J.F., Durairaj, P., Parr, M.K. and Bureik, M. Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1. Biol. Chem. 400 (2019) 625–628. [DOI] [PMID: 30465713]
[EC 1.14.14.139 created 2005 as EC 1.14.13.96, transferred 2018 to EC 1.14.14.139 (EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, incorporated 2020) , modified 2020]
 
 
EC 1.14.15.38
Accepted name: N,N-dimethyl phenylurea N-demethylase
Reaction: an N,N-dimethyl-N′-phenylurea compound + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = an N-methyl-N′-phenylurea compound + formaldehyde + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
Other name(s): pdmAB (gene names)
Systematic name: N,N-dimethyl-N′-phenylurea compound,NAD(P)H:oxygen oxidoreductase (formaldehyde-forming)
Comments: The enzyme, found in members of the Sphingobium genus, initiates the degradation of N,N-dimethyl-phenylurea herbicides by mono-N-demethylation. The catalytic unit contains a Rieske [2Fe-2S] iron-sulfur cluster, and catalyses the monooxygenation of a methyl group. The resulting N-methoxyl group is unstable and decomposes spontaneously to form formaldehyde. The enzyme associates with additional proteins (a reductase and a [3Fe-4S] type ferredoxin) that are involved in the transfer of electrons from NAD(P)H to the active site.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Gu, T., Zhou, C., Sorensen, S.R., Zhang, J., He, J., Yu, P., Yan, X. and Li, S. The novel bacterial N-demethylase PdmAB is responsible for the initial step of N,N-dimethyl-substituted phenylurea herbicide degradation. Appl. Environ. Microbiol. 79 (2013) 7846–7856. [PMID: 24123738]
[EC 1.14.15.38 created 2020]
 
 
EC 1.14.18.8
Transferred entry: 7α-hydroxycholest-4-en-3-one 12α-hydroxylase. Now included with EC 1.14.14.139, 5β-cholestane-3α,7α-diol 12α-hydroxylase
[EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, deleted 2020]
 
 
*EC 1.14.99.38
Accepted name: cholesterol 25-monooxygenase
Reaction: cholesterol + reduced acceptor + O2 = 25-hydroxycholesterol + acceptor + H2O
For diagram of cholic acid biosynthesis (sidechain), click here
Glossary: cholesterol = cholest-5-en-3β-ol
Other name(s): cholesterol 25-hydroxylase (ambiguous)
Systematic name: cholesterol,hydrogen-donor:oxygen oxidoreductase (25-hydroxylating)
Comments: Unlike most other sterol hydroxylases, this enzyme is not a cytochrome P-450. Instead, it uses diiron cofactors to catalyse the hydroxylation of hydrophobic substrates [1]. The diiron cofactor can be either Fe-O-Fe or Fe-OH-Fe and is bound to the enzyme through interactions with clustered histidine or glutamate residues [4,5]. In cell cultures, this enzyme down-regulates cholesterol synthesis and the processing of sterol regulatory element binding proteins (SREBPs). cf. EC 1.17.99.10, cholesterol C-25 hydroxylase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 60202-07-5
References:
1.  Lund, E.G., Kerr, T.A., Sakai, J., Li, W.P. and Russell, D.W. cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. J. Biol. Chem. 273 (1998) 34316–34327. [DOI] [PMID: 9852097]
2.  Chen, J.J., Lukyanenko, Y. and Hutson, J.C. 25-Hydroxycholesterol is produced by testicular macrophages during the early postnatal period and influences differentiation of Leydig cells in vitro. Biol. Reprod. 66 (2002) 1336–1341. [PMID: 11967195]
3.  Lukyanenko, Y., Chen, J.J. and Hutson, J.C. Testosterone regulates 25-hydroxycholesterol production in testicular macrophages. Biol. Reprod. 67 (2002) 1435–1438. [PMID: 12390873]
4.  Fox, B.G., Shanklin, J., Ai, J., Loehr, T.M. and Sanders-Loehr, J. Resonance Raman evidence for an Fe-O-Fe center in stearoyl-ACP desaturase. Primary sequence identity with other diiron-oxo proteins. Biochemistry 33 (1994) 12776–12786. [PMID: 7947683]
5.  Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]
[EC 1.14.99.38 created 2005, modified 2020]
 
 
EC 1.14.99.67
Accepted name: α-N-dichloroacetyl-p-aminophenylserinol N-oxygenase
Reaction: α-N-dichloroacetyl-p-aminophenylserinol + reduced acceptor + 2 O2 = chloramphenicol + acceptor + 2 H2O
Glossary: α-N-dichloroacetyl-p-aminophenylserinol = N-[(1R,2R)-1-(4-aminophenyl)-1,3-dihydroxypropan-2-yl]-2,2-dichloroacetamide
Other name(s): cmlI (gene name)
Systematic name: α-N-dichloroacetyl-p-aminophenylserinol,acceptor:oxygen oxidoreductase (N-hydroxylating)
Comments: The enzyme, isolated from the bacterium Streptomyces venezuelae, is involved in the biosynthesis of the antibiotic chloramphenicol. It contains a carboxylate-bridged binuclear non-heme iron cluster. The components of the native electron chain have not been identified, although the immediate donor is likely to be an iron-sulfur protein. The reaction mechanism involves formation of an extremely stable peroxo intermediate that catalyses three individual two-electron oxidations via a hydroxylamine and a nitroso intermediates without releasing the intermediates. cf. EC 1.14.99.68, 4-aminobenzoate N-oxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Lu, H., Chanco, E. and Zhao, H. CmlI is an N-oxygenase in the biosynthesis of chloramphenicol. Tetrahedron 68 (2012) 7651–7654. [DOI] [PMID: 24347692]
2.  Makris, T.M., Vu, V.V., Meier, K.K., Komor, A.J., Rivard, B.S., Munck, E., Que, L., Jr. and Lipscomb, J.D. An unusual peroxo intermediate of the arylamine oxygenase of the chloramphenicol biosynthetic pathway. J. Am. Chem. Soc. 137 (2015) 1608–1617. [DOI] [PMID: 25564306]
3.  Komor, A.J., Rivard, B.S., Fan, R., Guo, Y., Que, L., Jr. and Lipscomb, J.D. CmlI N-oxygenase catalyzes the final three steps in chloramphenicol biosynthesis without dissociation of intermediates. Biochemistry 56 (2017) 4940–4950. [DOI] [PMID: 28823151]
[EC 1.14.99.67 created 2020]
 
 
EC 1.14.99.68
Accepted name: 4-aminobenzoate N-oxygenase
Reaction: 4-aminobenzoate + reduced acceptor + 2 O2 = 4-nitrobenzoate + acceptor + 2 H2O
Glossary: 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
Other name(s): aurF (gene name)
Systematic name: 4-aminobenzoate,acceptor:oxygen oxidoreductase (N-hydroxylating)
Comments: The enzyme, characterized from the bacterium Streptomyces thioluteus, catalyses an early step in the biosynthesis of the antibiotic aureothin. It contains a carboxylate-bridged binuclear non-heme iron cluster. The native electron donor has not been identified, but is likely an iron-sulfur protein. The reaction mechanism involves formation of an extremely stable peroxo intermediate that catalyses three two-electron oxidations via a hydroxylamine and dihydroxylamine intermediates. cf. EC 1.14.99.67, N-[1-(4-aminophenyl)-1,3-dihydroxypropan-2-yl]-2,2-dichloroacetamide N-oxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  He, J. and Hertweck, C. Biosynthetic origin of the rare nitroaryl moiety of the polyketide antibiotic aureothin: involvement of an unprecedented N-oxygenase. J. Am. Chem. Soc. 126 (2004) 3694–3695. [DOI] [PMID: 15038705]
2.  Lee, J. and Zhao, H. Mechanistic studies on the conversion of arylamines into arylnitro compounds by aminopyrrolnitrin oxygenase: identification of intermediates and kinetic studies. Angew. Chem. Int. Ed. Engl. 45 (2006) 622–625. [DOI] [PMID: 16342311]
3.  Zocher, G., Winkler, R., Hertweck, C. and Schulz, G.E. Structure and action of the N-oxygenase AurF from Streptomyces thioluteus. J. Mol. Biol. 373 (2007) 65–74. [DOI] [PMID: 17765264]
4.  Choi, Y.S., Zhang, H., Brunzelle, J.S., Nair, S.K. and Zhao, H. In vitro reconstitution and crystal structure of p-aminobenzoate N-oxygenase (AurF) involved in aureothin biosynthesis. Proc. Natl. Acad. Sci. USA 105 (2008) 6858–6863. [DOI] [PMID: 18458342]
5.  Korboukh, V.K., Li, N., Barr, E.W., Bollinger, J.M., Jr. and Krebs, C. A long-lived, substrate-hydroxylating peroxodiiron(III/III) intermediate in the amine oxygenase, AurF, from Streptomyces thioluteus. J. Am. Chem. Soc. 131 (2009) 13608–13609. [DOI] [PMID: 19731912]
6.  Li, N., Korboukh, V.K., Krebs, C. and Bollinger, J.M., Jr. Four-electron oxidation of p-hydroxylaminobenzoate to p-nitrobenzoate by a peroxodiferric complex in AurF from Streptomyces thioluteus. Proc. Natl. Acad. Sci. USA 107 (2010) 15722–15727. [DOI] [PMID: 20798054]
[EC 1.14.99.68 created 2020]
 
 
EC 1.14.99.69
Accepted name: tRNA 2-(methylsulfanyl)-N6-isopentenyladenosine37 hydroxylase
Reaction: 2-(methylsulfanyl)-N6-prenyladenosine37 in tRNA + reduced acceptor + O2 = N6-[(2E)-4-hydroxy-3-methylbut-2-en-1-yl]-2-(methylsulfanyl)adenosine37 in tRNA + acceptor + H2O
Glossary: 2-(methylsulfanyl)-N6-prenyladenosine = N6-(3-methylbut-2-en-1-yl)-2-(methylsulfanyl)adenosine
Other name(s): miaE (gene name); tRNA 2-methylthio-N6-isopentenyl adenosine(37) hydroxylase; tRNA 2-(methylsulfanyl)-N6-dimethylallyladenosine37 hydroxylase
Systematic name: tRNA 2-(methylsulfanyl)-N6-prenyladenosine37,donor:oxygen 4-oxidoreductase (trans-hydroxylating)
Comments: The enzyme, found only within a small subset of facultative anaerobic bacteria, belongs to the nonheme diiron family. The enzyme from Salmonella typhimurium was shown to catalyse a stereoselective (E)-hydroxylation at the terminal C4-position of the prenyl group.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Persson, B.C. and Bjork, G.R. Isolation of the gene (miaE) encoding the hydroxylase involved in the synthesis of 2-methylthio-cis-ribozeatin in tRNA of Salmonella typhimurium and characterization of mutants. J. Bacteriol. 175 (1993) 7776–7785. [DOI] [PMID: 8253666]
2.  Persson, B.C., Olafsson, O., Lundgren, H.K., Hederstedt, L. and Bjork, G.R. The ms2io6A37 modification of tRNA in Salmonella typhimurium regulates growth on citric acid cycle intermediates. J. Bacteriol. 180 (1998) 3144–3151. [DOI] [PMID: 9620964]
3.  Corder, A.L., Subedi, B.P., Zhang, S., Dark, A.M., Foss, F.W., Jr. and Pierce, B.S. Peroxide-shunt substrate-specificity for the Salmonella typhimurium O2-dependent tRNA modifying monooxygenase (MiaE). Biochemistry 52 (2013) 6182–6196. [DOI] [PMID: 23906247]
[EC 1.14.99.69 created 2020]
 
 
EC 1.17.98.4
Accepted name: formate dehydrogenase (hydrogenase)
Reaction: formate + an [oxidized hydrogenase] = CO2 + a [reduced hydrogenase]
Other name(s): FDHH; FDH-H; FDH-O; formate dehydrogenase H; formate dehydrogenase O
Systematic name: formate:[oxidized hydrogenase] oxidoreductase
Comments: Formate dehydrogenase H is a cytoplasmic enzyme that oxidizes formate without oxygen transfer, transferring electrons to a hydrogenase. The two enzymes form the formate-hydrogen lyase complex [1]. The enzyme contains an [4Fe-4S] cluster, a selenocysteine residue and a molybdopterin cofactor [1].
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Axley, M.J., Grahame, D.A. and Stadtman, T.C. Escherichia coli formate-hydrogen lyase. Purification and properties of the selenium-dependent formate dehydrogenase component. J. Biol. Chem. 265 (1990) 18213–18218. [PMID: 2211698]
2.  Gladyshev, V.N., Boyington, J.C., Khangulov, S.V., Grahame, D.A., Stadtman, T.C. and Sun, P.D. Characterization of crystalline formate dehydrogenase H from Escherichia coli. Stabilization, EPR spectroscopy, and preliminary crystallographic analysis. J. Biol. Chem. 271 (1996) 8095–8100. [DOI] [PMID: 8626495]
3.  Khangulov, S.V., Gladyshev, V.N., Dismukes, G.C. and Stadtman, T.C. Selenium-containing formate dehydrogenase H from Escherichia coli: a molybdopterin enzyme that catalyzes formate oxidation without oxygen transfer. Biochemistry 37 (1998) 3518–3528. [DOI] [PMID: 9521673]
[EC 1.17.98.4 created 2010 as EC 1.1.99.33, transferred 2018 to EC 1.17.99.7, transferred 2020 to 1.17.98.4.]
 
 
EC 1.17.99.7
Transferred entry: formate dehydrogenase (acceptor). Now classified as EC 1.17.98.4, formate dehydrogenase (hydrogenase).
[EC 1.17.99.7 created 2010 as EC 1.1.99.33, transferred 2017 to EC 1.17.99.7, deleted 2020]
 
 
EC 1.17.99.9
Accepted name: heme a synthase
Reaction: ferroheme o + H2O + 2 acceptor = ferroheme a + 2 reduced acceptor (overall reaction)
(1a) ferroheme o + H2O + acceptor = ferroheme i + reduced acceptor
(1b) ferroheme i + H2O + acceptor = hydroxyferroheme i + reduced acceptor
(1c) hydroxyferroheme i = ferroheme a + H2O (spontaneous)
Other name(s): COX15 (gene name); ctaA (gene name)
Systematic name: ferroheme o:acceptor C-81-oxidoreductase (heme a-forming)
Comments: Contains a heme b cofactor. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a [2,4]. The electrons produced by the reaction are transferred to a heme b cofactor [6]. However, the electron acceptor that is used to restore the heme b cofactor to its oxidized state is still not known (both a thioredoxin-like protein and menaquinol have been proposed).
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Barros, M.H., Carlson, C.G., Glerum, D.M. and Tzagoloff, A. Involvement of mitochondrial ferredoxin and Cox15p in hydroxylation of heme O. FEBS Lett. 492 (2001) 133–138. [DOI] [PMID: 11248251]
2.  Brown, K.R., Allan, B.M., Do, P. and Hegg, E.L. Identification of novel hemes generated by heme A synthase: evidence for two successive monooxygenase reactions. Biochemistry 41 (2002) 10906–10913. [DOI] [PMID: 12206660]
3.  Brown, K.R., Brown, B.M., Hoagland, E., Mayne, C.L. and Hegg, E.L. Heme A synthase does not incorporate molecular oxygen into the formyl group of heme A. Biochemistry 43 (2004) 8616–8624. [DOI] [PMID: 15236569]
4.  Hederstedt, L., Lewin, A. and Throne-Holst, M. Heme A synthase enzyme functions dissected by mutagenesis of Bacillus subtilis CtaA. J. Bacteriol. 187 (2005) 8361–8369. [DOI] [PMID: 16321940]
5.  Hederstedt, L. Heme A biosynthesis. Biochim. Biophys. Acta 1817 (2012) 920–927. [DOI] [PMID: 22484221]
6.  Niwa, S., Takeda, K., Kosugi, M., Tsutsumi, E., Mogi, T. and Miki, K. Crystal structure of heme A synthase from Bacillus subtilis. Proc. Natl. Acad. Sci. USA 115 (2018) 11953–11957. [DOI] [PMID: 30397130]
[EC 1.17.99.9 created 2020]
 
 
EC 1.17.99.10
Accepted name: steroid C-25 hydroxylase
Reaction: cholest-4-en-3-one + acceptor + H2O = 25-hydroxycholest-4-en-3-one + reduced acceptor
For diagram of cholic acid biosynthesis (sidechain), click here
Other name(s): s25dA1 (gene name); s25dA1B3 (gene name); s25dA1C3 (gene name); cholesterol C-25 dehydrogenase; steroid C-25 dehydrogenase
Systematic name: cholest-4-en-3-one:acceptor oxidoreductase (25-hydroxylating)
Comments: The enzyme, characterized from the bacterium Sterolibacterium denitrificans, participates in the anaerobic degradation of cholesterol. The enzyme can accept several substrates including vitamin D3. The enzyme contains a bis(guanylyl molybdopterin) cofactor, five [Fe-S] clusters, and one heme b. cf. EC 1.14.99.38, cholesterol 25-monooxygenase, an oxygen-requiring eukaryotic enzyme that catalyses a similar transformation.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Dermer, J. and Fuchs, G. Molybdoenzyme that catalyzes the anaerobic hydroxylation of a tertiary carbon atom in the side chain of cholesterol. J. Biol. Chem. 287 (2012) 36905–36916. [DOI] [PMID: 22942275]
2.  Rugor, A., Tataruch, M., Staron, J., Dudzik, A., Niedzialkowska, E., Nowak, P., Hogendorf, A., Michalik-Zym, A., Napruszewska, D.B., Jarzebski, A., Szymanska, K., Bialas, W. and Szaleniec, M. Regioselective hydroxylation of cholecalciferol, cholesterol and other sterol derivatives by steroid C25 dehydrogenase. Appl. Microbiol. Biotechnol. 101 (2017) 1163–1174. [DOI] [PMID: 27726023]
3.  Rugor, A., Wojcik-Augustyn, A., Niedzialkowska, E., Mordalski, S., Staron, J., Bojarski, A. and Szaleniec, M. Reaction mechanism of sterol hydroxylation by steroid C25 dehydrogenase - Homology model, reactivity and isoenzymatic diversity. J. Inorg. Biochem. 173 (2017) 28–43. [DOI] [PMID: 28482186]
4.  Jacoby, C., Eipper, J., Warnke, M., Tiedt, O., Mergelsberg, M., Stark, H.J., Daus, B., Martin-Moldes, Z., Zamarro, M.T., Diaz, E. and Boll, M. Four molybdenum-dependent steroid C-25 hydroxylases: heterologous overproduction, role in steroid degradation, and application for 25-hydroxyvitamin D3 synthesis. mBio 9:e00694-18 (2018). [DOI] [PMID: 29921665]
[EC 1.17.99.10 created 2020]
 
 
EC 1.17.99.11
Accepted name: 3-oxo-Δ1-steroid hydratase/dehydrogenase
Reaction: a 3-oxo-Δ1-steroid + H2O + acceptor = a steroid 1,3-dione + reduced acceptor (overall reaction)
(1a) a 3-oxo-Δ1-steroid + H2O = a 1-hydroxy-3-oxo-steroid
(1b) a 1-hydroxy-3-oxo-steroid + acceptor = a steroid 1,3-dione + reduced acceptor
Glossary: Δ1-dihydrotestosterone = 17β-hydroxy-5α-androst-1-en-3-one
Other name(s): atcABC (gene names)
Systematic name: 3-oxo-Δ1-steroid:acceptor 1-oxidoreductase
Comments: A molybdenum enzyme. The enzyme, characterized from the bacterium Steroidobacter denitrificans, is involved in the anaetrobic degradation of steroids. It is specific to 3-oxo-Δ1-steroids such as androsta-1-ene-3,17-dione and Δ1-dihydrotestosterone and does not act on 3-oxo-Δ4-steroids.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Yang, F.C., Chen, Y.L., Tang, S.L., Yu, C.P., Wang, P.H., Ismail, W., Wang, C.H., Ding, J.Y., Yang, C.Y., Yang, C.Y. and Chiang, Y.R. Integrated multi-omics analyses reveal the biochemical mechanisms and phylogenetic relevance of anaerobic androgen biodegradation in the environment. ISME J. 10 (2016) 1967–1983. [DOI] [PMID: 26872041]
[EC 1.17.99.11 created 2020]
 
 
EC 2.1.1.373
Accepted name: 2-hydroxy-4-(methylsulfanyl)butanoate S-methyltransferase
Reaction: S-adenosyl-L-methionine + (2R)-2-hydroxy-4-(methylsulfanyl)butanoate = S-adenosyl-L-homocysteine + (2R)-4-(dimethylsulfaniumyl)-2-hydroxybutanoate
Other name(s): dsyB (gene name); methylthiohydroxybutyrate methyltransferase; MTHB methyltransferase
Systematic name: S-adenosyl-L-methionine:(2R)-2-hydroxy-4-(methylsulfanyl)butanoate S-methyltransferase
Comments: The enzyme, characterized from the marine bacterium Labrenzia aggregata, participates in the biosynthesis of dimethylsulfoniopropanoate (DMSP). A eukaryotic enzyme that shares little sequence similarity with the bacterial enzyme was identified in many marine phytoplankton species.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Summers, P.S., Nolte, K.D., Cooper, A.J.L., Borgeas, H., Leustek, T., Rhodes, D. and Hanson, A.D. Identification and stereospecificity of the first three enzymes of 3-dimethylsulfoniopropionate biosynthesis in a chlorophyte alga. Plant Physiol. 116 (1998) 369–378. [DOI]
2.  Curson, A.R., Liu, J., Bermejo Martinez, A., Green, R.T., Chan, Y., Carrion, O., Williams, B.T., Zhang, S.H., Yang, G.P., Bulman Page, P.C., Zhang, X.H. and Todd, J.D. Dimethylsulfoniopropionate biosynthesis in marine bacteria and identification of the key gene in this process. Nat. Microbiol. 2:17009 (2017). [DOI] [PMID: 28191900]
3.  Kageyama, H., Tanaka, Y., Shibata, A., Waditee-Sirisattha, R. and Takabe, T. Dimethylsulfoniopropionate biosynthesis in a diatom Thalassiosira pseudonana: Identification of a gene encoding MTHB-methyltransferase. Arch. Biochem. Biophys. 645 (2018) 100–106. [DOI] [PMID: 29574051]
4.  Curson, A.RJ., Williams, B.T., Pinchbeck, B.J., Sims, L.P., Martinez, A.B., Rivera, P.PL., Kumaresan, D., Mercade, E., Spurgin, L.G., Carrion, O., Moxon, S., Cattolico, R.A., Kuzhiumparambil, U., Guagliardo, P., Clode, P.L., Raina, J.B. and Todd, J.D. DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton. Nat. Microbiol. 3 (2018) 430–439. [DOI] [PMID: 29483657]
[EC 2.1.1.373 created 2020]
 
 
EC 2.1.1.374
Accepted name: 2-heptyl-1-hydroxyquinolin-4(1H)-one methyltransferase
Reaction: S-adenosyl-L-methionine + 2-heptyl-1-hydroxyquinolin-4(1H)-one = S-adenosyl-L-homocysteine + 2-heptyl-1-methoxyquinolin-4(1H)-one
Other name(s): htm (gene name)
Systematic name: S-adenosyl-L-methionine:2-heptyl-1-hydroxyquinolin-4(1H)-one methyltransferase
Comments: The enzyme, found in mycobacteria, is a member of a family of heterocyclic toxin methyltransferases. It is involved in defense against several antimicrobial natural compounds and drugs. 4-Hydroxyquinolin-2(1H)-one, 2-heptylquinolin-4(1H)-one, 2-heptyl-3-hydroxyquinolin-4(1H)-one (the "Pseudomonas quinolone signal", PQS) and the flavonol quercetin are also O-methylated, albeit with lower activity [2]. The enzyme also N-methylates the bactericidal compound 3-methyl-1-oxo-2-[3-oxo-3-(pyrrolidin-1-yl)propyl]-1,5-dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile [1].
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Warrier, T., Kapilashrami, K., Argyrou, A., Ioerger, T.R., Little, D., Murphy, K.C., Nandakumar, M., Park, S., Gold, B., Mi, J., Zhang, T., Meiler, E., Rees, M., Somersan-Karakaya, S., Porras-De Francisco, E., Martinez-Hoyos, M., Burns-Huang, K., Roberts, J., Ling, Y., Rhee, K.Y., Mendoza-Losana, A., Luo, M. and Nathan, C.F. N-methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 113 (2016) E4523–E4530. [DOI] [PMID: 27432954]
2.  Sartor, P., Bock, J., Hennecke, U., Thierbach, S. and Fetzner, S. Modification of the Pseudomonas aeruginosa toxin 2-heptyl-1-hydroxyquinolin-4(1H)-one and other secondary metabolites by methyltransferases from mycobacteria. FEBS J. (2020) . [DOI] [PMID: 33064871]
[EC 2.1.1.374 created 2020]
 
 
EC 2.2.1.13
Accepted name: apulose-4-phosphate transketolase
Reaction: apulose 4-phosphate + D-glyceraldehyde 3-phosphate = D-xylulose 5-phosphate + glycerone phosphate
Glossary: apulose = 1,3,4-trihydroxy-3-(hydroxymethyl)butan-2-one
Other name(s): aptAB (gene names)
Systematic name: apulose-4-phosphate:D-glyceraldehyde-3-phosphate glycolaldehydetransferase
Comments: The enzyme, characterized from several bacterial species, is involved in a catabolic pathway for D-apiose.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696–705. [DOI] [PMID: 29867142]
[EC 2.2.1.13 created 2020]
 
 
*EC 2.3.1.179
Accepted name: β-ketoacyl-[acyl-carrier-protein] synthase II
Reaction: a (Z)-hexadec-9-enoyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = a (Z)-3-oxooctadec-11-enoyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein]
Glossary: palmitoleoyl-[acyl-carrier protein] = (Z)-hexadec-9-enoyl-[acyl-carrier protein]
cis-vaccenoyl-[acyl-carrier protein] = (Z)-octadec-11-enoyl-[acyl-carrier protein]
Other name(s): KASII; KAS II; FabF; 3-oxoacyl-acyl carrier protein synthase II; β-ketoacyl-ACP synthase II
Systematic name: (Z)-hexadec-9-enoyl-[acyl-carrier protein]:malonyl-[acyl-carrier protein] C-acyltransferase (decarboxylating)
Comments: Involved in the dissociated (or type II) fatty acid biosynthesis system that occurs in plants and bacteria. While the substrate specificity of this enzyme is very similar to that of EC 2.3.1.41, β-ketoacyl-[acyl-carrier-protein] synthase I, it differs in that palmitoleoyl-[acyl-carrier protein] is not a good substrate of EC 2.3.1.41 but is an excellent substrate of this enzyme [1,2]. The fatty-acid composition of Escherichia coli changes as a function of growth temperature, with the proportion of unsaturated fatty acids increasing with lower growth temperature. This enzyme controls the temperature-dependent regulation of fatty-acid composition, with mutants lacking this acivity being deficient in the elongation of palmitoleate to cis-vaccenate at low temperatures [3,4].
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 1048648-42-5
References:
1.  D'Agnolo, G., Rosenfeld, I.S. and Vagelos, P.R. Multiple forms of β-ketoacyl-acyl carrier protein synthetase in Escherichia coli. J. Biol. Chem. 250 (1975) 5289–5294. [PMID: 237914]
2.  Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr.. Structural, enzymatic, and genetic studies of β-ketoacyl-acyl carrier protein synthases I and II of Escherichia coli. J. Biol. Chem. 255 (1980) 11949–11956. [PMID: 7002930]
3.  Price, A.C., Rock, C.O. and White, S.W. The 1.3-Angstrom-resolution crystal structure of β-ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae. J. Bacteriol. 185 (2003) 4136–4143. [DOI] [PMID: 12837788]
4.  Garwin, J.L., Klages, A.L. and Cronan, J.E., Jr. β-Ketoacyl-acyl carrier protein synthase II of Escherichia coli. Evidence for function in the thermal regulation of fatty acid synthesis. J. Biol. Chem. 255 (1980) 3263–3265. [PMID: 6988423]
5.  Magnuson, K., Carey, M.R. and Cronan, J.E., Jr. The putative fabJ gene of Escherichia coli fatty acid synthesis is the fabF gene. J. Bacteriol. 177 (1995) 3593–3595. [DOI] [PMID: 7768872]
6.  Cronan, J.E., Jr. and Rock, C.O. Biosynthesis of membrane lipids. In: Neidhardt, F.C. (Ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 1, ASM Press, Washington, DC, 1996, pp. 612–636.
[EC 2.3.1.179 created 2006, modified 2020]
 
 
*EC 2.3.1.190
Accepted name: acetoin dehydrogenase system
Reaction: acetoin + CoA + NAD+ = acetaldehyde + acetyl-CoA + NADH + H+
Other name(s): acetoin dehydrogenase complex; acetoin dehydrogenase enzyme system; AoDH ES; acetoin dehydrogenase
Systematic name: acetyl-CoA:acetoin O-acetyltransferase
Comments: Requires thiamine diphosphate. It belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.104, pyruvate dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.2.1.25, branched-chain α-keto acid dehydrogenase system, and EC 1.4.1.27, glycine cleavage system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3).
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Priefert, H., Hein, S., Kruger, N., Zeh, K., Schmidt, B. and Steinbuchel, A. Identification and molecular characterization of the Alcaligenes eutrophus H16 aco operon genes involved in acetoin catabolism. J. Bacteriol. 173 (1991) 4056–4071. [DOI] [PMID: 2061286]
2.  Oppermann, F.B. and Steinbuchel, A. Identification and molecular characterization of the aco genes encoding the Pelobacter carbinolicus acetoin dehydrogenase enzyme system. J. Bacteriol. 176 (1994) 469–485. [DOI] [PMID: 8110297]
3.  Kruger, N., Oppermann, F.B., Lorenzl, H. and Steinbuchel, A. Biochemical and molecular characterization of the Clostridium magnum acetoin dehydrogenase enzyme system. J. Bacteriol. 176 (1994) 3614–3630. [DOI] [PMID: 8206840]
4.  Huang, M., Oppermann, F.B. and Steinbuchel, A. Molecular characterization of the Pseudomonas putida 2,3-butanediol catabolic pathway. FEMS Microbiol. Lett. 124 (1994) 141–150. [DOI] [PMID: 7813883]
5.  Huang, M., Oppermann-Sanio, F.B. and Steinbuchel, A. Biochemical and molecular characterization of the Bacillus subtilis acetoin catabolic pathway. J. Bacteriol. 181 (1999) 3837–3841. [DOI] [PMID: 10368162]
[EC 2.3.1.190 created 2010, modified 2020]
 
 
EC 2.3.2.36
Accepted name: RING-type E3 ubiquitin transferase (cysteine targeting)
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine
Glossary: RING = Really Interesting New Gene
Other name(s): RING E3 ligase (misleading)
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (thioester bond-froming; RING-type)
Comments: This relatively rare subpopulation of RING-type E3 ubiquitin transferases (cf. EC 2.3.2.27), found in mammals and herpes viruses, can transfer ubiquitin to a cysteine residue in target proteins. Additional ubiquitin molecules are polymerized on top of the initial ubiquitin molecule by formation of an isopeptide linkage with lysine48 in the pre-attached ubiquitin [2].
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Cadwell, K. and Coscoy, L. Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase. Science 309 (2005) 127–130. [DOI] [PMID: 15994556]
2.  Wang, Y.J., Bian, Y., Luo, J., Lu, M., Xiong, Y., Guo, S.Y., Yin, H.Y., Lin, X., Li, Q., Chang, C.CY., Chang, T.Y., Li, B.L. and Song, B.L. Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation. Nat. Cell Biol. 19 (2017) 808–819. [DOI] [PMID: 28604676]
3.  Zhou, Z.S., Li, M.X., Liu, J., Jiao, H., Xia, J.M., Shi, X.J., Zhao, H., Chu, L., Liu, J., Qi, W., Luo, J. and Song, B.L. Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2. Nat. Commun. 11:379 (2020). [DOI] [PMID: 31953408]
[EC 2.3.2.36 created 2020]
 
 
*EC 2.4.2.29
Accepted name: tRNA-guanosine34 preQ1 transglycosylase
Reaction: guanine34 in tRNA + 7-aminomethyl-7-carbaguanine = 7-aminomethyl-7-carbaguanine34 in tRNA + guanine
For diagram of queuine biosynthesis, click here
Glossary: 7-aminomethyl-7-carbaguanine = preQ1 = 7-aminomethyl-7-deazaguanine
7-cyano-7-carbaguanine = preQ0 = 7-cyano-7-deazaguanine
Other name(s): guanine insertion enzyme (ambiguous); tRNA transglycosylase (ambiguous); Q-insertase (ambiguous); transfer ribonucleate glycosyltransferase (ambiguous); tRNA guanine34 transglycosidase (ambiguous); TGT (ambiguous); transfer ribonucleic acid guanine34 transglycosylase (ambiguous)
Systematic name: tRNA-guanosine34:7-aminomethyl-7-deazaguanine tRNA-D-ribosyltransferase
Comments: Certain prokaryotic and eukaryotic tRNAs contain the modified base queuine at position 34. In eubacteria, which produce queuine de novo, the enzyme catalyses the exchange of guanine with the queuine precursor preQ1, which is ultimately modified to queuosine [5]. The enzyme can also use an earlier intermediate, preQ0, to replace guanine in unmodified tRNATyr and tRNAAsn [1]. This enzyme acts after EC 1.7.1.13, preQ1 synthase, in the queuine-biosynthesis pathway. cf. EC 2.4.2.64, tRNA-guanosine34 queuine transglycosylase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 72162-89-1
References:
1.  Okada, N., Noguchi, S., Kasai, H., Shindo-Okada, N., Ohgi, T., Goto, T. and Nishimura, S. Novel mechanism of post-transcriptional modification of tRNA. Insertion of bases of Q precursors into tRNA by a specific tRNA transglycosylase reaction. J. Biol. Chem. 254 (1979) 3067–3073. [PMID: 372186]
2.  Noguchi, S., Nishimura, Y., Hirota, Y. and Nishimura, S. Isolation and characterization of an Escherichia coli mutant lacking tRNA-guanine transglycosylase. Function and biosynthesis of queuosine in tRNA. J. Biol. Chem. 257 (1982) 6544–6550. [PMID: 6804468]
3.  Chong, S., Curnow, A.W., Huston, T.J. and Garcia, G.A. tRNA-guanine transglycosylase from Escherichia coli is a zinc metalloprotein. Site-directed mutagenesis studies to identify the zinc ligands. Biochemistry 34 (1995) 3694–3701. [DOI] [PMID: 7893665]
4.  Goodenough-Lashua, D.M. and Garcia, G.A. tRNA-guanine transglycosylase from E. coli: a ping-pong kinetic mechanism is consistent with nucleophilic catalysis. Bioorg. Chem. 31 (2003) 331–344. [DOI] [PMID: 12877882]
5.  Todorov, K.A. and Garcia, G.A. Role of aspartate 143 in Escherichia coli tRNA-guanine transglycosylase: alteration of heterocyclic substrate specificity. Biochemistry 45 (2006) 617–625. [DOI] [PMID: 16401090]
[EC 2.4.2.29 created 1984, modified 2007, modified 2012, modified 2020]
 
 
EC 2.4.2.64
Accepted name: tRNA-guanosine34 queuine transglycosylase
Reaction: guanine34 in tRNA + queuine = queuine34 in tRNA + guanine
For diagram of queuine biosynthesis, click here
Glossary: queuine = base Q = 2-amino-5-({[(1S,4S,5R)-4,5-dihydroxycyclopent-2-en-1-yl]amino}methyl)-1,7-dihydropyrrolo[3,2-e]pyrimidin-4-one
Other name(s): QTRT1 (gene name); QTRT2 (gene name); TGT (ambiguous); guanine insertion enzyme (ambiguous); tRNA transglycosylase (ambiguous); Q-insertase (ambiguous); queuine34 transfer ribonucleate ribosyltransferase; transfer ribonucleate glycosyltransferase (ambiguous); tRNA guanine34 transglycosidase (ambiguous); queuine tRNA-ribosyltransferase; [tRNA]-guanine34:queuine tRNA-D-ribosyltransferase; transfer ribonucleic acid guanine34 transglycosylase (ambiguous)
Systematic name: tRNA-guanosine34:queuine tRNA-D-ribosyltransferase
Comments: Certain prokaryotic and eukaryotic tRNAs contain the modified base queuine at position 34. In eukaryotes and a small number of prokaryotes queuine is salvaged and incorporated into tRNA directly via a base-exchange reaction, replacing guanine. cf. EC 2.4.2.29, tRNA-guanosine34 preQ1 transglycosylase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 72162-89-1
References:
1.  Howes, N.K. and Farkas, W.R. Studies with a homogeneous enzyme from rabbit erythrocytes catalyzing the insertion of guanine into tRNA. J. Biol. Chem. 253 (1978) 9082–9087. [PMID: 721832]
2.  Shindo-Okada, N., Okada, N., Ohgi, T., Goto, T. and Nishimura, S. Transfer ribonucleic acid guanine transglycosylase isolated from rat liver. Biochemistry 19 (1980) 395–400. [DOI] [PMID: 6986171]
3.  Boland, C., Hayes, P., Santa-Maria, I., Nishimura, S. and Kelly, V.P. Queuosine formation in eukaryotic tRNA occurs via a mitochondria-localized heteromeric transglycosylase. J. Biol. Chem. 284 (2009) 18218–18227. [DOI] [PMID: 19414587]
4.  Yuan, Y., Zallot, R., Grove, T.L., Payan, D.J., Martin-Verstraete, I., Sepic, S., Balamkundu, S., Neelakandan, R., Gadi, V.K., Liu, C.F., Swairjo, M.A., Dedon, P.C., Almo, S.C., Gerlt, J.A. and de Crecy-Lagard, V. Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens. Proc. Natl. Acad. Sci. USA 116 (2019) 19126–19135. [DOI] [PMID: 31481610]
[EC 2.4.2.64 created 2020 (EC 2.4.2.29 created 1984, modified 2007, modified 2012, part transferred 2020 to EC 2.4.2.64)]
 
 
*EC 2.5.1.25
Accepted name: tRNA-uridine aminocarboxypropyltransferase
Reaction: S-adenosyl-L-methionine + a uridine in tRNA = S-methyl-5′-thioadenosine + a 3-[(3S)-3-amino-3-carboxypropyl]uridine in tRNA
Other name(s): S-adenosyl-L-methionine:tRNA-uridine 3-(3-amino-3-carboxypropyl)transferase; tapT (gene name); DTWD1 (gene name); DTWD2 (gene name); S-adenosyl-L-methionine:uridine47 in tRNAPhe 3-[(3S)-3-amino-3-carboxypropyl]transferase
Systematic name: S-adenosyl-L-methionine:uridine in tRNA 3-[(3S)-3-amino-3-carboxypropyl]transferase
Comments: 3-[(3S)-3-amino-3-carboxypropyl]uridine (acp3U) is a highly conserved modification found in tRNA core region in bacteria and eukaryotes that confers thermal stability on tRNA. The enzyme from the bacterium Escherichia coli catalyses the modification of uridine47 in the V-loop of tRNAs for Arg2, Ile1, Ile2, Ile2v, Lys, Met, Phe, Val2A, and Val2B. The human homologs DTWD1 and DTWD2 are responsible for acp3U formation at positions 20 and 20a, respectively, in the D-loop of several cytoplasmic tRNAs.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Nishimura, S., Taya, Y., Kuchino, Y. and Ohashi, Z. Enzymatic synthesis of 3-(3-amino-3-carboxypropyl)uridine in Escherichia coli phenylalanine transfer RNA: transfer of the 3-amino-acid-3-carboxypropyl group from S-adenosylmethionine. Biochem. Biophys. Res. Commun. 57 (1974) 702–708. [DOI] [PMID: 4597321]
2.  Takakura, M., Ishiguro, K., Akichika, S., Miyauchi, K. and Suzuki, T. Biogenesis and functions of aminocarboxypropyluridine in tRNA. Nat. Commun. 10:5542 (2019). [DOI] [PMID: 31804502]
3.  Meyer, B., Immer, C., Kaiser, S., Sharma, S., Yang, J., Watzinger, P., Weiss, L., Kotter, A., Helm, M., Seitz, H.M., Kotter, P., Kellner, S., Entian, K.D. and Wohnert, J. Identification of the 3-amino-3-carboxypropyl (acp) transferase enzyme responsible for acp3U formation at position 47 in Escherichia coli tRNAs. Nucleic Acids Res. 48 (2020) 1435–1450. [DOI] [PMID: 31863583]
[EC 2.5.1.25 created 1984, modified 2014, modified 2020]
 
 
EC 2.5.1.153
Accepted name: adenosine tuberculosinyltransferase
Reaction: tuberculosinyl diphosphate + adenosine = 1-tuberculosinyladenosine + diphosphate
Glossary: tuberculosinyl diphosphate = halima-5,13-dien-15-yl diphosphate
Other name(s): Rv3378c (locus name)
Systematic name: tuberculosinyl-diphosphate:adenosine tuberculosinyltransferase
Comments: The enzyme, characterized from the bacterial pathogen Mycobacterium tuberculosis, produces 1-tuberculosinyladenosine, an unusual terpene nucleoside that acts as a phagolysosome disruptor by neutralizing the pH, resulting in swelling of the lysosome and obliteration of its multilamellar structure.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Layre, E., Lee, H.J., Young, D.C., Martinot, A.J., Buter, J., Minnaard, A.J., Annand, J.W., Fortune, S.M., Snider, B.B., Matsunaga, I., Rubin, E.J., Alber, T. and Moody, D.B. Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c. Proc. Natl. Acad. Sci. USA 111 (2014) 2978–2983. [DOI] [PMID: 24516143]
2.  Young, D.C., Layre, E., Pan, S.J., Tapley, A., Adamson, J., Seshadri, C., Wu, Z., Buter, J., Minnaard, A.J., Coscolla, M., Gagneux, S., Copin, R., Ernst, J.D., Bishai, W.R., Snider, B.B. and Moody, D.B. In vivo biosynthesis of terpene nucleosides provides unique chemical markers of Mycobacterium tuberculosis infection. Chem. Biol. 22 (2015) 516–526. [DOI] [PMID: 25910243]
3.  Buter, J., Cheng, T.Y., Ghanem, M., Grootemaat, A.E., Raman, S., Feng, X., Plantijn, A.R., Ennis, T., Wang, J., Cotton, R.N., Layre, E., Ramnarine, A.K., Mayfield, J.A., Young, D.C., Jezek Martinot, A., Siddiqi, N., Wakabayashi, S., Botella, H., Calderon, R., Murray, M., Ehrt, S., Snider, B.B., Reed, M.B., Oldfield, E., Tan, S., Rubin, E.J., Behr, M.A., van der Wel, N.N., Minnaard, A.J. and Moody, D.B. Mycobacterium tuberculosis releases an antacid that remodels phagosomes. Nat. Chem. Biol. 15 (2019) 889–899. [DOI] [PMID: 31427817]
[EC 2.5.1.153 created 2011 as EC 3.1.7.8 and EC 3.1.7.9, transferred 2020 to EC 2.5.1.153]
 
 
*EC 2.7.7.69
Accepted name: GDP-L-galactose/GDP-D-glucose: hexose 1-phosphate guanylyltransferase
Reaction: (1) GDP-β-L-galactose + α-D-mannose 1-phosphate = β-L-galactose 1-phosphate + GDP-α-D-mannose
(2) GDP-α-D-glucose + α-D-mannose 1-phosphate = α-D-glucose 1-phosphate + GDP-α-D-mannose
Other name(s): VTC2; VTC5; GDP-L-galactose phosphorylase
Systematic name: GDP-β-L-galactose/GDP-α-D-glucose:hexose 1-phosphate guanylyltransferase
Comments: This plant enzyme catalyses the conversion of GDP-β-L-galactose and GDP-α-D-glucose to β-L-galactose 1-phosphate and α-D-glucose 1-phosphate, respectively. The enzyme can use inorganic phosphate as the co-substrate, but several hexose 1-phosphates, including α-D-mannose 1-phosphate, α-D-glucose 1-phosphate, and α-D-galactose 1-phosphate, are better guanylyl acceptors. The enzyme's activity on GDP-β-L-galactose is crucial for the biosynthesis of L-ascorbate.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Linster, C.L., Gomez, T.A., Christensen, K.C., Adler, L.N., Young, B.D., Brenner, C. and Clarke, S.G. Arabidopsis VTC2 encodes a GDP-L-galactose phosphorylase, the last unknown enzyme in the Smirnoff-Wheeler pathway to ascorbic acid in plants. J. Biol. Chem. 282 (2007) 18879–18885. [DOI] [PMID: 17462988]
2.  Dowdle, J., Ishikawa, T., Gatzek, S., Rolinski, S. and Smirnoff, N. Two genes in Arabidopsis thaliana encoding GDP-L-galactose phosphorylase are required for ascorbate biosynthesis and seedling viability. Plant J. 52 (2007) 673–689. [DOI] [PMID: 17877701]
3.  Wolucka, B.A. and Van Montagu, M. The VTC2 cycle and the de novo biosynthesis pathways for vitamin C in plants: an opinion. Phytochemistry 68 (2007) 2602–2613. [DOI] [PMID: 17950389]
4.  Laing, W.A., Wright, M.A., Cooney, J. and Bulley, S.M. The missing step of the L-galactose pathway of ascorbate biosynthesis in plants, an L-galactose guanyltransferase, increases leaf ascorbate content. Proc. Natl. Acad. Sci. USA 104 (2007) 9534–9539. [DOI] [PMID: 17485667]
5.  Linster, C.L., Adler, L.N., Webb, K., Christensen, K.C., Brenner, C. and Clarke, S.G. A second GDP-L-galactose phosphorylase in arabidopsis en route to vitamin C. Covalent intermediate and substrate requirements for the conserved reaction. J. Biol. Chem. 283 (2008) 18483–18492. [DOI] [PMID: 18463094]
6.  Muller-Moule, P. An expression analysis of the ascorbate biosynthesis enzyme VTC2. Plant Mol. Biol. 68 (2008) 31–41. [DOI] [PMID: 18516687]
[EC 2.7.7.69 created 2010, modified 2020]
 
 
*EC 2.7.7.88
Accepted name: GDP polyribonucleotidyltransferase
Reaction: (5′)pppAACA-[mRNA] + GDP = diphosphate + G(5′)pppAACA-[mRNA] (overall reaction)
(1a) (5′)pppAACA-[mRNA] + [protein L]-L-histidine = diphosphate + [protein L]-L-histidyl-(5′)phosphonato-AACA-[mRNA] + H2O
(1b) [protein L]-L-histidyl-(5′)phosphonato-AACA-[mRNA] + GDP + H2O = [protein L]-L-histidine + G(5′)pppAACA-[mRNA]
Other name(s): PRNTase; 5′-triphospho-mRNA:GDP 5′-phosphopolyribonucleotidyltransferase [G(5′)ppp-mRNA-forming]
Systematic name: (5′)pppAACA-[mRNA]:GDP 5′-phosphopolyribonucleotidyltransferase [(5′)pppAACA-[mRNA]-forming]
Comments: The enzyme from non-segmented negative strain (NNS) viruses (e.g. rhabdoviruses and lyssaviruses) is specific for mRNAs with sequences starting with AACA. cf. EC 2.7.7.50, mRNA guanylyltransferase.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Ogino, T. and Banerjee, A.K. Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus. Mol. Cell 25 (2007) 85–97. [DOI] [PMID: 17218273]
2.  Ogino, T. and Banerjee, A.K. Formation of guanosine(5′)tetraphospho(5′)adenosine cap structure by an unconventional mRNA capping enzyme of vesicular stomatitis virus. J. Virol. 82 (2008) 7729–7734. [DOI] [PMID: 18495767]
3.  Ogino, T., Yadav, S.P. and Banerjee, A.K. Histidine-mediated RNA transfer to GDP for unique mRNA capping by vesicular stomatitis virus RNA polymerase. Proc. Natl. Acad. Sci. USA 107 (2010) 3463–3468. [DOI] [PMID: 20142503]
4.  Ogino, T. and Banerjee, A.K. The HR motif in the RNA-dependent RNA polymerase L protein of Chandipura virus is required for unconventional mRNA-capping activity. J. Gen. Virol. 91 (2010) 1311–1314. [DOI] [PMID: 20107017]
5.  Ogino, T. and Banerjee, A.K. An unconventional pathway of mRNA cap formation by vesiculoviruses. Virus Res. 162 (2011) 100–109. [DOI] [PMID: 21945214]
6.  Ogino, M., Ito, N., Sugiyama, M. and Ogino, T. The rabies virus L protein catalyzes mRNA capping with GDP polyribonucleotidyltransferase activity. Viruses 8:144 (2016). [DOI] [PMID: 27213429]
[EC 2.7.7.88 created 2015, modified 2020]
 
 
EC 3.1.1.115
Accepted name: D-apionolactonase
Reaction: D-apionolactone + H2O = D-apionate
Glossary: D-apionolactone = (3R,4R)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-one
Other name(s): apnL (gene name)
Systematic name: D-apionolactone lactonohydrolase
Comments: The enzyme, characterized from several bacterial species, is involved in a catabolic pathway for D-apiose.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696–705. [DOI] [PMID: 29867142]
[EC 3.1.1.115 created 2020]
 
 
EC 3.1.3.31
Deleted entry: nucleotidase. The activity may be that of an acid phosphatase.
[EC 3.1.3.31 created 1972 (EC 3.1.3.30 created 1972, incorporated 1992), deleted 2020]
 
 
EC 3.1.7.8
Transferred entry: tuberculosinol synthase. Now known to be partial activity of EC 2.5.1.153, adenosine tuberculosinyltransferase.
[EC 3.1.7.8 created 2011, deleted 2020]
 
 
EC 3.1.7.9
Transferred entry: isotuberculosinol synthase. Now known to be partial activity of EC 2.5.1.153, adenosine tuberculosinyltransferase.
[EC 3.1.7.9 created 2011, deleted 2020]
 
 
EC 3.5.1.136
Accepted name: N,N′-diacetylchitobiose non-reducing end deacetylase
Reaction: N,N′-diacetylchitobiose + H2O = β-D-glucosaminyl-(1→4)-N-acetyl-D-glucosamine + acetate
Other name(s): diacetylchitobiose deacetylase (ambiguous); cda (gene name)
Systematic name: N,N′-diacetylchitobiose non-reducing end acetylhydrolase
Comments: The enzyme, characterized from the archaeons Thermococcus kodakarensis and Pyrococcus horikoshii, deacetylates the non-reducing residue of N,N′-diacetylchitobiose, the end product of the archaeal chitinase, to produce β-D-glucosaminyl-(1→4)-N-acetyl-D-glucosamine. This is in contrast to EC 3.5.1.105, chitin disaccharide deacetylase, which deacetylates N,N′-diacetylchitobiose at the reducing residue to produce N-acetyl-β-D-glucosaminyl-(1→4)-D-glucosamine.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Tanaka, T., Fukui, T., Fujiwara, S., Atomi, H. and Imanaka, T. Concerted action of diacetylchitobiose deacetylase and exo-β-D-glucosaminidase in a novel chitinolytic pathway in the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. J. Biol. Chem. 279 (2004) 30021–30027. [DOI] [PMID: 15136574]
2.  Mine, S., Ikegami, T., Kawasaki, K., Nakamura, T. and Uegaki, K. Expression, refolding, and purification of active diacetylchitobiose deacetylase from Pyrococcus horikoshii. Protein Expr. Purif. 84 (2012) 265–269. [DOI] [PMID: 22713621]
3.  Nakamura, T., Yonezawa, Y., Tsuchiya, Y., Niiyama, M., Ida, K., Oshima, M., Morita, J. and Uegaki, K. Substrate recognition of N,N′-diacetylchitobiose deacetylase from Pyrococcus horikoshii. J. Struct. Biol. 195:S1047-8477( (2016). [DOI] [PMID: 27456364]
[EC 3.5.1.136 created 2020]
 
 
EC 3.7.1.27
Transferred entry: neryl diphosphate diphosphatase. Now EC 3.1.7.13, neryl diphosphate diphosphatase.
[EC 3.7.1.27 created 2020, deleted 2021]
 
 
EC 5.1.3.44
Accepted name: mannose 2-epimerase
Reaction: β-D-mannopyranose = β-D-glucopyranose
Systematic name: β-D-mannopyranose 2-epimerase
Comments: The enzyme, characterized from multiple bacterial species, catalyses the interconversion between β-D-glucopyranose and β-D-mannopyranose through proton abstraction-addition at the C2 position.
Links to other databases: BRENDA, EXPASY, KEGG
References:
1.  Saburi, W., Sato, S., Hashiguchi, S., Muto, H., Iizuka, T. and Mori, H. Enzymatic characteristics of D-mannose 2-epimerase, a new member of the acylglucosamine 2-epimerase superfamily. Appl. Microbiol. Biotechnol. 103 (2019) 6559–6570. [DOI] [PMID: 31201453]
[EC 5.1.3.44 created 2020]
 
 
EC 5.3.1.36
Accepted name: D-apiose isomerase
Reaction: D-apiose = apulose
Glossary: apulose = 1,3,4-trihydroxy-3-(hydroxymethyl)butan-2-one
Other name(s): apsI (gene name)
Systematic name: D-apiose isomerase
Comments: The enzyme, characterized from several bacterial species, is involved in a catabolic pathway for D-apiose.
Links to other databases: BRENDA, EXPASY, KEGG, PDB
References:
1.  Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696–705. [DOI] [PMID: 29867142]
[EC 5.3.1.36 created 2020]
 
 


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