Proposed Changes to the Enzyme List

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

Contents

For diagram of reaction click here

Other name(s): retinol (vitamin A₁) dehydrogenase; MDR; microsomal retinol dehydrogenase; retinol dehydrogenase (misleading); retinal reductase; retinene reductase; epidermal retinol dehydrogenase 2; SDR16C5 (gene name); RDH16 (gene name)

Systematic name: all-trans retinol:NAD⁺ oxidoreductase

Comments: The enzyme recognizes all-trans-retinol and all-trans-retinal as substrates and exhibits a strong preference for NAD⁺/NADH as cofactors. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein (CRBP1), but has higher affinity for the bound form [2]. No activity with 11-cis-retinol or 11-cis-retinal (c.f. EC 1.1.1.315, 11-cis retinol dehydrogenase). Also active with 3α-hydroxysteroids [2].

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 9033-53-8

References:

1. Koen, A.L. and Shaw, C.R. Retinol and alcohol dehydrogenases in retina and liver. Biochim. Biophys. Acta 128 (1966) 48-54. [PMID: 5972368]

2. Gough, W.H., VanOoteghem, S., Sint, T. and Kedishvili, N.Y. cDNA cloning and characterization of a new human microsomal NAD⁺-dependent dehydrogenase that oxidizes all-trans-retinol and 3α-hydroxysteroids. J. Biol. Chem. 273 (1998) 19778-19785. [PMID: 9677409]

3. Matsuzaka, Y., Okamoto, K., Tsuji, H., Mabuchi, T., Ozawa, A., Tamiya, G. and Inoko, H. Identification of the hRDH-E2 gene, a novel member of the SDR family, and its increased expression in psoriatic lesion. Biochem. Biophys. Res. Commun. 297 (2002) 1171-1180. [PMID: 12372410]

4. Lee, S.A., Belyaeva, O.V. and Kedishvili, N.Y. Biochemical characterization of human epidermal retinol dehydrogenase 2. Chem. Biol. Interact. 178 (2009) 182-187. [PMID: 18926804]

*EC 1.1.1.302

Accepted name: 2,5-diamino-6-(ribosylamino)-4(3H)-pyrimidinone 5'-phosphate reductase

Reaction: 2,5-diamino-6-(5-phospho-D-ribitylamino)pyrimidin-4(3H)-one + NAD(P)⁺ = 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + NAD(P)H + H⁺

For diagram of reaction click here

Other name(s): 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate reductase; MjaRED; MJ0671 (gene name)

Systematic name: 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one:NAD(P)⁺ oxidoreductase

Comments: The reaction proceeds in the opposite direction. A step in riboflavin biosynthesis, NADPH and NADH function equally well as reductant. Differs from EC 1.1.1.193 [5-amino-6-(5-phosphoribosylamino)uracil reductase] since it does not catalyse the reduction of 5-amino-6-ribosylaminopyrimidine-2,4(1H,3H)-dione 5'-phosphate [1].

Links to other databases: BRENDA, EXPASY, KEGG

References:

1. Graupner, M., Xu, H. and White, R.H. The pyrimidine nucleotide reductase step in riboflavin and F₄₂₀ biosynthesis in archaea proceeds by the eukaryotic route to riboflavin. J. Bacteriol. 184 (2002) 1952-1957. [PMID: 11889103]

2. Chatwell, L., Krojer, T., Fidler, A., Romisch, W., Eisenreich, W., Bacher, A., Huber, R. and Fischer, M. Biosynthesis of riboflavin: structure and properties of 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate reductase of Methanocaldococcus jannaschii. J. Mol. Biol. 359 (2006) 1334-1351. [PMID: 16730025]

EC 1.1.1.315

Accepted name: 11-cis-retinol dehydrogenase

Reaction: 11-cis-retinol—[retinal-binding-protein] + NAD⁺ = 11-cis-retinal—[retinol-binding-protein] + NADH + H⁺

For diagram of reaction click here

Glossary: 11-cis-retinal = 11-cis-retinaldehyde

Other name(s): RDH5 (gene name)

Systematic name: 11-cis-retinol:NAD⁺ oxidoreductase

Comments: This enzyme, abundant in the retinal pigment epithelium, catalyses the reduction of 11-cis-retinol to 11-cis-retinal [1] while the substrate is bound to the retinal-binding protein [4]. This is a crucial step in the regeneration of 11-cis-retinal, the chromophore of rhodopsin. The enzyme can also accept other cis forms of retinol [2].

References:

1. Simon, A., Hellman, U., Wernstedt, C. and Eriksson, U. The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases. J. Biol. Chem. 270 (1995) 1107-1112. [PMID: 7836368]

2. Wang, J., Chai, X., Eriksson, U. and Napoli, J.L. Activity of human 11-cis-retinol dehydrogenase (Rdh5) with steroids and retinoids and expression of its mRNA in extra-ocular human tissue. Biochem. J. 338 (1999) 23-27. [PMID: 9931293]

3. Liden, M., Romert, A., Tryggvason, K., Persson, B. and Eriksson, U. Biochemical defects in 11-cis-retinol dehydrogenase mutants associated with fundus albipunctatus. J. Biol. Chem. 276 (2001) 49251-49257. [PMID: 11675386]

4. Wu, Z., Yang, Y., Shaw, N., Bhattacharya, S., Yan, L., West, K., Roth, K., Noy, N., Qin, J. and Crabb, J.W. Mapping the ligand binding pocket in the cellular retinaldehyde binding protein. J. Biol. Chem. 278 (2003) 12390-12396. [PMID: 12536149]

EC 1.2.1.82

Accepted name: β-apo-4'-carotenal oxygenase

Reaction: 4'-apo-β,ψ-caroten-4'-al + NAD⁺ + H₂O = neurosporaxanthin + NADH + 2 H⁺

For diagram of reaction click here

Glossary: neurosporaxanthin = 4'-apo-β,ψ-caroten-4'-oic acid

Other name(s): β-apo-4'-carotenal dehydrogenase; YLO-1; carD (gene name)

Systematic name: 4'-apo-β,ψ-carotenal:NAD⁺ oxidoreductase

Comments: Neurosporaxanthin is responsible for the orange color of of Neurospora.

References:

1. Estrada, A.F., Youssar, L., Scherzinger, D., Al-Babili, S. and Avalos, J. The ylo-1 gene encodes an aldehyde dehydrogenase responsible for the last reaction in the Neurospora carotenoid pathway. Mol. Microbiol. 69 (2008) 1207-1220. [PMID: 18627463]

2. Diaz-Sanchez, V., Estrada, A.F., Trautmann, D., Al-Babili, S. and Avalos, J. The gene carD encodes the aldehyde dehydrogenase responsible for neurosporaxanthin biosynthesis in Fusarium fujikuroi. FEBS J. 278 (2011) 3164-3176. [PMID: 21749649]

EC 1.4.9 With a copper protein as acceptor

EC 1.4.9.1

Accepted name: methylamine dehydrogenase (amicyanin)

Reaction: methylamine + H₂O + amicyanin = formaldehyde + ammonia + reduced amicyanin

Glossary: TTQ = tryptophan tryptophylquinone
amicyanin = an electron-transfer protein containing a type-1 copper site.

Other name(s): amine dehydrogenase; primary-amine dehydrogenase; amine: (acceptor) oxidoreductase (deaminating); primary-amine:(acceptor) oxidoreductase (deaminating)

Systematic name: methylamine:amicyanin oxidoreductase (deaminating)

Comments: Contains tryptophan tryptophylquinone (TTQ) cofactor. The enzyme oxidizes aliphatic monoamines and diamines, histamine and ethanolamine, but not secondary and tertiary amines, quaternary ammonium salts or aromatic amines.

References:

1. De Beer, R., Duine, J.A., Frank, J., Jr. and Large, P.J. The prosthetic group of methylamine dehydrogenase from Pseudomonas AM1: evidence for a quinone structure. Biochim. Biophys. Acta 622 (1980) 370-374. [PMID: 6246962]

2. Eady, R.R. and Large, P.J. Purification and properties of an amine dehydrogenase from Pseudomonas AM1 and its role in growth on methylamine. Biochem. J. 106 (1968) 245-255. [PMID: 4388687]

3. Eady, R.R. and Large, P.J. Microbial oxidation of amines. Spectral and kinetic properties of the primary amine dehydrogenase of Pseudomonas AM1. Biochem. J. 123 (1971) 757-771. [PMID: 5124384]

4. Cavalieri, C., Biermann, N., Vlasie, M.D., Einsle, O., Merli, A., Ferrari, D., Rossi, G.L. and Ubbink, M. Structural comparison of crystal and solution states of the 138 kDa complex of methylamine dehydrogenase and amicyanin from Paracoccus versutus. Biochemistry 47 (2008) 6560-6570. [PMID: 18512962]

5. Meschi, F., Wiertz, F., Klauss, L., Cavalieri, C., Blok, A., Ludwig, B., Heering, H.A., Merli, A., Rossi, G.L. and Ubbink, M. Amicyanin transfers electrons from methylamine dehydrogenase to cytochrome c-551i via a ping-pong mechanism, not a ternary complex. J. Am. Chem. Soc. 132 (2010) 14537-14545. [PMID: 20873742]

EC 1.4.9.2

Accepted name: aralkylamine dehydrogenase (azurin)

Reaction: ArCH₂NH₂ + H₂O + 2 azurin = ArCHO + NH₃ + 2 reduced azurin

Glossary: azurin = an electron-transfer protein containing a type-1 copper site

Other name(s): aromatic amine dehydrogenase; arylamine dehydrogenase; tyramine dehydrogenase; aralkylamine:(acceptor) oxidoreductase (deaminating)

Systematic name: aralkylamine:azurin oxidoreductase (deaminating)

Comments: Phenazine methosulfate can act as acceptor. Acts on aromatic amines and, more slowly, on some long-chain aliphatic amines, but not on methylamine or ethylamine

References:

1. Iwaki, M., Yagi, T., Horiike, K., Saeki, Y., Ushijima, T. and Nozaki, M. Crystallization and properties of aromatic amine dehydrogenase from Pseudomonas sp. Arch. Biochem. Biophys. 220 (1983) 253-262. [PMID: 6830237]

2. Hyun, Y.L. and Davidson, V.L. Electron transfer reactions between aromatic amine dehydrogenase and azurin. Biochemistry 34 (1995) 12249-12254. [PMID: 7547967]

3. Hyun, Y.L., Zhu, Z. and Davidson, V.L. Gated and ungated electron transfer reactions from aromatic amine dehydrogenase to azurin. J. Biol. Chem. 274 (1999) 29081-29086. [PMID: 10506161]

4. Davidson, V.L. Electron transfer in quinoproteins. Arch. Biochem. Biophys. 428 (2004) 32-40. [PMID: 15234267]

5. Sukumar, N., Chen, Z.W., Ferrari, D., Merli, A., Rossi, G.L., Bellamy, H.D., Chistoserdov, A., Davidson, V.L. and Mathews, F.S. Crystal structure of an electron transfer complex between aromatic amine dehydrogenase and azurin from Alcaligenes faecalis. Biochemistry 45 (2006) 13500-13510. [PMID: 17087503]

[EC 1.4.98.1 Transferred entry: amine dehydrogenase. Now EC 1.4.9.1, methylamine dehydrogenase (amicyanin) (EC 1.4.98.1 created 1978 as EC 1.4.99.3, modified 1986, transferred 2011 to EC 1.4.98.1, deleted 2011)]

[EC 1.4.99.4 Transferred entry: aralkylamine dehydrogenase. Now EC 1.4.9.2, aralkylamine dehydrogenase (azurin) (EC 1.4.99.4 created 1986, deleted 2011)]

EC 1.6.5.10

Accepted name: NADPH dehydrogenase (quinone)

Reaction: NADPH + H⁺ + a quinone = NADP⁺ + a quinol

Other name(s): reduced nicotinamide adenine dinucleotide phosphate (quinone) dehydrogenase; NADPH oxidase; NADPH₂ dehydrogenase (quinone)

Systematic name: NADPH:(quinone-acceptor) oxidoreductase

Comments: A flavoprotein [1, 2]. The enzyme from Escherichia coli is specific for NADPH and is most active with quinone derivatives and ferricyanide as electron acceptors [3]. Menaquinone can act as acceptor. The enzyme from hog liver is inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol [1].

References:

1. Koli, A.K., Yearby, C., Scott, W. and Donaldson, K.O. Purification and properties of three separate menadione reductases from hog liver. J. Biol. Chem. 244 (1969) 621-629. [PMID: 4388793]

2. Hayashi, M., Hasegawa, K., Oguni, Y. and Unemoto, T. Characterization of FMN-dependent NADH-quinone reductase induced by menadione in Escherichia coli. Biochim. Biophys. Acta 1035 (1990) 230-236. [PMID: 2118386]

3. Hayashi, M., Ohzeki, H., Shimada, H. and Unemoto, T. NADPH-specific quinone reductase is induced by 2-methylene-4-butyrolactone in Escherichia coli. Biochim. Biophys. Acta 1273 (1996) 165-170. [PMID: 8611590]

[EC 1.6.99.6 Transferred entry: Transferred to EC 1.6.5.10, NADPH dehydrogenase (quinone) (EC 1.6.99.6 created 1972, deleted 2011)]

*EC 1.13.11.16

Accepted name: 3-carboxyethylcatechol 2,3-dioxygenase

Reaction: (1) 3-(2,3-dihydroxyphenyl)propanoate + O₂ = 2-hydroxy-6-oxonona-2,4-diene-1,9-dioate
(2) (2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate + O₂ = 2-hydroxy-6-oxonona-2,4,7-triene-1,9-dioate

Glossary: (2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate = trans-2,3-dihydroxycinnamate

Other name(s): 2,3-dihydroxy-β-phenylpropionic dioxygenase; 2,3-dihydroxy-β-phenylpropionate oxygenase; 3-(2,3-dihydroxyphenyl)propanoate:oxygen 1,2-oxidoreductase

Systematic name: 3-(2,3-dihydroxyphenyl)propanoate:oxygen 1,2-oxidoreductase (decyclizing)

Comments: An iron protein. This enzyme catalyses a step in the pathway of phenylpropanoid compounds degradation.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 105503-63-7

References:

1. Dagley, S., Chapman, P.J. and Gibson, D.T. The metabolism of β-phenylpropionic acid by an Achromobacter. Biochem. J. 97 (1965) 643-650. [PMID: 5881653]

2. Díaz, E., Ferrández, A. and García, J.L. Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12. J. Bacteriol. 180 (1998) 2915-2923. [PMID: 9603882]

*EC 1.13.11.26

Accepted name: peptide-tryptophan 2,3-dioxygenase

Reaction: [protein]-L-tryptophan + O₂ = [protein]-N-formyl-L-kynurenine

Glossary: N-formyl-L-kynurenine = (2S)-2-amino-4-[2-(formamido)phenyl]-4-oxobutanoic acid

Other name(s): pyrrolooxygenase; peptidyltryptophan 2,3-dioxygenase; tryptophan pyrrolooxygenase

Systematic name: [protein]-L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)

Comments: Also acts on tryptophan.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 37256-64-7

References:

1. Frydman, R.B., Tomaro, M.L. and Frydman, B. Pyrrolooxygenase: its action on tryptophan-containing enzymes and peptides. Biochim. Biophys. Acta 284 (1972) 80-89. [PMID: 4403729]

2. Camoretti-Mercado, B. and Frydman, R.B. Separation of tryptophan pyrrolooxygenase into three molecular forms. A study of their substrate specificities using tryptophyl-containing peptides and proteins. Eur. J. Biochem. 156 (1986) 317-325. [PMID: 3699018]

EC 1.13.11.59

Accepted name: torulene dioxygenase

Reaction: torulene + O₂ = 4'-apo-β,ψ-caroten-4'-al + 3-methylbut-2-enal

For diagram of reaction click here

Glossary: torulene = 3',4'-didehydro-β,ψ-carotene

Other name(s): CAO-2; CarT

Systematic name: torulene:oxygen oxidoreductase

Comments: It is assumed that 3-methylbut-2-enal is formed. The enzyme cannot cleave the saturated 3',4'-bond of γ-carotene which implies that a 3',4'-double bond is neccessary for this reaction.

References:

1. Prado-Cabrero, A., Estrada, A.F., Al-Babili, S. and Avalos, J. Identification and biochemical characterization of a novel carotenoid oxygenase: elucidation of the cleavage step in the Fusarium carotenoid pathway. Mol. Microbiol. 64 (2007) 448-460. [PMID: 17493127]

2. Saelices, L., Youssar, L., Holdermann, I., Al-Babili, S. and Avalos, J. Identification of the gene responsible for torulene cleavage in the Neurospora carotenoid pathway. Mol. Genet. Genomics 278 (2007) 527-537. [PMID: 17610084]

3. Estrada, A.F., Maier, D., Scherzinger, D., Avalos, J. and Al-Babili, S. Novel apocarotenoid intermediates in Neurospora crassa mutants imply a new biosynthetic reaction sequence leading to neurosporaxanthin formation. Fungal Genet. Biol. 45 (2008) 1497-1505. [PMID: 18812228]

EC 1.13.12.19

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

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

Other name(s): ethylene-forming enzyme; EFE

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

Comments: This is one of two simultaneous reactions catalysed by the enzyme, which is responsible for ethylene production in bacteria of the Pseudomonas syringae group. In the other reaction [EC 1.14.11.34, 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming)] the enzyme catalyses the mono-oxygenation of both 2-oxoglutarate and L-arginine, forming succinate, carbon dioxide and L-hydroxyarginine, which is subsequently cleaved into guanidine and (S)-1-pyrroline-5-carboxylate. The enzymes catalyse two cycles of the ethylene-forming reaction for each cycle of the succinate-forming reaction, so that the stoichiometry of the products ethylene and succinate is 2:1.

References:

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

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

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

EC 1.14.11.34

Accepted name: 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming)

Reaction: 2-oxoglutarate + L-arginine + O₂ = succinate + CO₂ + guanidine + (S)-1-pyrroline-5-carboxylate + H₂O (overall reaction)
(1a) 2-oxoglutarate + L-arginine + O₂ = succinate + CO₂ + L-hydroxyarginine
(1b) L-hydroxyarginine = guanidine + (S)-1-pyrroline-5-carboxylate + H₂O

Other name(s): ethylene-forming enzyme; EFE

Systematic name: L-arginine,2-oxoglutarate:oxygen oxidoreductase (succinate-forming)

Comments: This is one of two simultaneous reactions catalysed by the enzyme, which is responsible for ethylene production in bacteria of the Pseudomonas syringae group. In the other reaction [EC 1.13.12.19, 2-oxoglutarate dioxygenase (ethylene-forming)] the enzyme catalyses the dioxygenation of 2-oxoglutarate forming ethylene and three molecules of carbon dioxide. The enzyme catalyses two cycles of the ethylene-forming reaction for each cycle of the succinate-forming reaction, so that the stoichiometry of the products ethylene and succinate is 2:1.

References:

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

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

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

*EC 1.14.12.19

Accepted name: 3-phenylpropanoate dioxygenase

Reaction: (1) 3-phenylpropanoate + NADH + H⁺ + O₂ = 3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate + NAD⁺
(2) (2E)-3-phenylprop-2-enoate + NADH + H⁺ + O₂ = (2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate + NAD⁺

For diagram of reaction, click here or click here

Glossary: (2E)-3-phenylprop-2-enoate = trans-cinnamate
(2E)-3-(2,3-dihydroxyphenyl)prop-2-enoate = trans-2,3-dihydroxycinnamate

Other name(s): HcaA1A2CD; Hca dioxygenase; 3-phenylpropionate dioxygenase

Systematic name: 3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating)

Comments: This enzyme catalyses a step in the pathway of phenylpropanoid compounds degradation. It catalyses the insertion of both atoms of molecular oxygen into positions 2 and 3 of the phenyl ring of 3-phenylpropanoate or (2E)-3-phenylprop-2-enoate.

Links to other databases: BRENDA, EXPASY, KEGG, UM-BBD

References:

1. Díaz, E., Ferrández, A. and García, J.L. Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12. J. Bacteriol. 180 (1998) 2915-2923. [PMID: 9603882]

2. Burlingame, R. and Chapman, P.J. Catabolism of phenylpropionic acid and its 3-hydroxy derivative by Escherichia coli. J. Bacteriol. 155 (1983) 113-121. [PMID: 6345502]

[EC 1.14.13.3 Transferred entry: 4-hydroxyphenylacetate 3-monooxygenase. Now EC 1.14.14.9, 4-hydroxyphenylacetate 3-monooxygenase. (EC 1.14.13.3 created 1972, deleted 2011)]

EC 1.14.13.131

Accepted name: dimethyl-sulfide monooxygenase

Reaction: dimethyl sulfide + O₂ + NADH + H⁺ = methanethiol + formaldehyde + NAD⁺ + H₂O

Other name(s): dimethylsulfide monooxygenase

Systematic name: dimethyl sulfide,NADH:oxygen oxidoreductase

Comments: The enzyme has lower activity with diethyl sulfide and other short-chain alkyl methyl sulfides. Its activity is stimulated by combined addition of FMN, and, after depletion of cations, of Mg²⁺ and Fe²⁺. The enzyme from Hyphomicrobium is a two component system that includes an FMN-dependent reductase subunit and a monooxygenase subunit.

References:

1. De Bont, J.A.M., Van Dijken, J.P. and Harder, W. Dimethyl sulphoxide and dimethyl sulphide as a carbon, sulphur and energy source for growth of Hyphomicrobium S. J. Gen. Microbiol. 127 (1981) 315-323.

2. Boden, R., Borodina, E., Wood, A.P., Kelly, D.P., Murrell, J.C. and Schafer, H. Purification and characterization of dimethylsulfide monooxygenase from Hyphomicrobium sulfonivorans. J. Bacteriol. 193 (2011) 1250-1258. [PMID: 21216999]

EC 1.14.13.132

Accepted name: squalene monooxygenase

Reaction: squalene + NADPH + H⁺ + O₂ = (3S)-2,3-epoxy-2,3-dihydrosqualene + NADP⁺ + H₂O

For diagram of reaction click here

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

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

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

References:

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

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

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

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

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

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

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

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

EC 1.14.14.9

Accepted name: 4-hydroxyphenylacetate 3-monooxygenase

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

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

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

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

References:

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

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

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

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

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

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

[EC 1.14.99.7 Transferred entry: squalene monooxygenase. Transferred to EC 1.14.13.132, squalene monooxygenase. (EC 1.14.99.7 created 1961 as EC 1.99.1.13, transferred 1965 to EC 1.14.1.3, part transferred 1972 to EC 1.14.99.7 rest to EC 5.4.99.7, deleted 2011)]

*EC 1.17.1.4

Accepted name: xanthine dehydrogenase

Reaction: xanthine + NAD⁺ + H₂O = urate + NADH + H⁺

For diagram of reaction click here

Glossary: 4-mercuribenzoate = (4-carboxylatophenyl)mercury

Other name(s): NAD⁺-xanthine dehydrogenase; xanthine-NAD⁺ oxidoreductase; xanthine/NAD⁺ oxidoreductase; xanthine oxidoreductase

Systematic name: xanthine:NAD⁺ oxidoreductase

Comments: Acts on a variety of purines and aldehydes, including hypoxanthine. The mammalian enzyme can also convert all-trans retinol to all-trans-retinoate, while the substrate is bound to a retinoid-binding protein [14]. The enzyme from eukaryotes contains [2Fe-2S], FAD and a molybdenum centre. The mammalian enzyme predominantly exists as the NAD-dependent dehydrogenase (EC 1.17.1.4). During purification the enzyme is largely converted to an O₂-dependent form, xanthine oxidase (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [2,6,8,15] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [2,7,15].

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9054-84-6

References:

1. Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133-138. [PMID: 6960894]

2. Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739-745. [PMID: 4342395]

3. Parzen, S.D. and Fox, A.S. Purification of xanthine dehydrogenase from Drosophila melanogaster. Biochim. Biophys. Acta 92 (1964) 465-471. [PMID: 14264879]

4. Rajagopalan, K.V. and Handler, P. Purification and properties of chicken liver xanthine dehydrogenase. J. Biol. Chem. 242 (1967) 4097-4107. [PMID: 4294045]

5. Smith, S.T., Rajagopalan, K.V. and Handler, P. Purification and properties of xanthine dehydroganase from Micrococcus lactilyticus. J. Biol. Chem. 242 (1967) 4108-4117. [PMID: 6061702]

6. Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254-260. [PMID: 3459393]

7. Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564-1570. [PMID: 3294898]

8. Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O₂-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179-183. [PMID: 2610112]

9. Parschat, K., Canne, C., Hüttermann, J., Kappl, R. and Fetzner, S. Xanthine dehydrogenase from Pseudomonas putida 86: specificity, oxidation-reduction potentials of its redox-active centers, and first EPR characterization. Biochim. Biophys. Acta 1544 (2001) 151-165. [PMID: 11341925]

10. Ichida, K., Amaya, Y., Noda, K., Minoshima, S., Hosoya, T., Sakai, O., Shimizu, N. and Nishino, T. Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene 133 (1993) 279-284. [PMID: 8224915]

11. Enroth, C., Eger, B.T., Okamoto, K., Nishino, T., Nishino, T. and Pai, E.F. Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc. Natl. Acad. Sci. USA 97 (2000) 10723-10728. [PMID: 11005854]

12. Truglio, J.J., Theis, K., Leimkuhler, S., Rappa, R., Rajagopalan, K.V. and Kisker, C. Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure 10 (2002) 115-125. [PMID: 11796116]

13. Hille, R. The mononuclear molybdenum enzymes. Chem. Rev. 96 (1996) 2757-2816. [PMID: 11848841]

14. Taibi, G., Di Gaudio, F. and Nicotra, C.M. Xanthine dehydrogenase processes retinol to retinoic acid in human mammary epithelial cells. J. Enzyme Inhib. Med. Chem. 23 (2008) 317-327. [PMID: 18569334]

15. Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278-3289. [PMID: 18513323]

*EC 1.17.3.2

Accepted name: xanthine oxidase

Reaction: xanthine + H₂O + O₂ = urate + H₂O₂

For diagram of reaction, click here

Glossary: 4-mercuribenzoate = (4-carboxylatophenyl)mercury

Other name(s): hypoxanthine oxidase; hypoxanthine:oxygen oxidoreductase; Schardinger enzyme; xanthine oxidoreductase; hypoxanthine-xanthine oxidase; xanthine:O₂ oxidoreductase; xanthine:xanthine oxidase

Systematic name: xanthine:oxygen oxidoreductase

Comments: An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H₂O + 2 O₂ = ROH + 2 O₂^.- + 2 H⁺. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O₂-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].

Links to other databases: BRENDA, EXPASY, KEGG, PDB, UM-BBD, CAS registry number: 9002-17-9

References:

1. Avis, P.G., Bergel, F. and Bray, R.C. Cellular constituents. The chemistry of xanthine oxidase. Part I. The preparation of a crystalline xanthine oxidase from cow's milk. J. Chem. Soc. (Lond.) (1955) 1100-1105.

2. Battelli, M.G. and Lorenzoni, E. Purification and properties of a new glutathione-dependent thiol:disulphide oxidoreductase from rat liver. Biochem. J. 207 (1982) 133-138. [PMID: 6960894]

3. Bray, R.C. Xanthine oxidase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 533-556.

4. Della Corte, E. and Stirpe, F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem. J. 126 (1972) 739-745. [PMID: 4342395]

5. Ikegami, T. and Nishino, T. The presence of desulfo xanthine dehydrogenase in purified and crude enzyme preparations from rat liver. Arch. Biochem. Biophys. 247 (1986) 254-260. [PMID: 3459393]

6. Engerson, T.D., McKelvey, T.G., Rhyne, D.B., Boggio, E.B., Snyder, S.J. and Jones, H.P. Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J. Clin. Invest. 79 (1987) 1564-1570. [PMID: 3294898]

7. Saito, T., Nishino, T. and Tsushima, K. Interconversion between NAD-dependent and O₂-dependent types of rat liver xanthine dehydrogenase and difference in kinetic and redox properties between them. Adv. Exp. Med. Biol. 253B (1989) 179-183. [PMID: 2610112]

8. Carpani, G., Racchi, M., Ghezzi, P., Terao, M. and Garattini, E. Purification and characterization of mouse liver xanthine oxidase. Arch. Biochem. Biophys. 279 (1990) 237-241. [PMID: 2350174]

9. Eger, B.T., Okamoto, K., Enroth, C., Sato, M., Nishino, T., Pai, E.F. and Nishino, T. Purification, crystallization and preliminary X-ray diffraction studies of xanthine dehydrogenase and xanthine oxidase isolated from bovine milk. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 1656-1658. [PMID: 11092937]

10. Nishino, T., Okamoto, K., Eger, B.T., Pai, E.F. and Nishino, T. Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 275 (2008) 3278-3289. [PMID: 18513323]

EC 1.20.2 With a cytochrome as acceptor

EC 1.20.2.1

Accepted name: arsenate reductase (cytochrome c)

Reaction: arsenite + H₂O + 2 oxidized cytochrome c = arsenate + 2 reduced cytochrome c + 2 H⁺

Other name(s): arsenite oxidase (ambiguous)

Systematic name: arsenite:cytochrome c oxidoreductase

Comments: A molybdoprotein containing iron-sulfur clusters. Isolated from α-proteobacteria. Unlike EC 1.20.9.1, arsenate reductase (azurin), it does not use azurin as acceptor.

References:

1. vanden Hoven, R.N. and Santini, J.M. Arsenite oxidation by the heterotroph Hydrogenophaga sp. str. NT-14: the arsenite oxidase and its physiological electron acceptor. Biochim. Biophys. Acta 1656 (2004) 148-155. [PMID: 15178476]

2. Santini, J.M., Kappler, U., Ward, S.A., Honeychurch, M.J., vanden Hoven, R.N. and Bernhardt, P.V. The NT-26 cytochrome c₅₅₂ and its role in arsenite oxidation. Biochim. Biophys. Acta 1767 (2007) 189-196. [PMID: 17306216]

3. Branco, R., Francisco, R., Chung, A.P. and Morais, P.V. Identification of an aox system that requires cytochrome c in the highly arsenic-resistant bacterium Ochrobactrum tritici SCII24. Appl. Environ. Microbiol. 75 (2009) 5141-5147. [PMID: 19525272]

4. Lieutaud, A., van Lis, R., Duval, S., Capowiez, L., Muller, D., Lebrun, R., Lignon, S., Fardeau, M.L., Lett, M.C., Nitschke, W. and Schoepp-Cothenet, B. Arsenite oxidase from Ralstonia sp. 22: characterization of the enzyme and its interaction with soluble cytochromes. J. Biol. Chem. 285 (2010) 20433-20441. [PMID: 20421652]

EC 1.20.9 With a copper protein as acceptor

EC 1.20.9.1

Accepted name: arsenate reductase (azurin)

Reaction: arsenite + H₂O + 2 oxidized azurin = arsenate + 2 reduced azurin + 2 H⁺

For diagram of reaction click here

Glossary: Azurin is a blue copper protein found in many bacteria, which undergoes oxidation-reduction between Cu(I) and Cu(II), and transfers single electrons between enzymes.

Other name(s): arsenite oxidase (ambiguous)

Systematic name: arsenite:azurin oxidoreductase

Comments: Contains a molybdopterin centre comprising two molybdopterin guanosine dinucleotide cofactors bound to molybdenum, a [3Fe-4S] cluster and a Rieske-type [2Fe-2S] cluster. Isolated from β-proteobacteria. Also uses a c-type cytochrome or O₂ as acceptors.

References:

1. Anderson, G.L., Williams, J. and Hille, R. The purification and characterization of arsenite oxidase from Alcaligenes faecalis, a molybdenum-containing hydroxylase. J. Biol. Chem. 267 (1992) 23674-23682. [PMID: 1331097]

2. Ellis, P.J., Conrads, T., Hille, R. and Kuhn, P. Crystal structure of the 100 kDa arsenite oxidase from Alcaligenes faecalis in two crystal forms at 1.64 Å and 2.03 Å. Structure 9 (2001) 125-132. [PMID: 11250197]

[EC 1.20.98.1 Transferred entry: arsenate reductase (azurin). Now EC 1.20.9.1, arsenate reductase (azurin) (EC 1.20.98.1 created 2001, deleted 2011)]

*EC 2.1.1.46

Accepted name: isoflavone 4'-O-methyltransferase

Reaction: S-adenosyl-L-methionine + a 4'-hydroxyisoflavone = S-adenosyl-L-homocysteine + a 4'-methoxyisoflavone

For diagram of reaction click here or click here

Other name(s): 4'-hydroxyisoflavone methyltransferase; isoflavone methyltransferase; isoflavone O-methyltransferase

Systematic name: S-adenosyl-L-methionine:4'-hydroxyisoflavone 4'-O-methyltransferase

Comments: Requires Mg²⁺ for activity. The enzyme catalyses the methylation of daidzein and genistein. It does not methylate naringenin, apigenin, luteolin or kaempferol.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 55071-80-2

References:

1. Wengenmayer, H., Ebel, J. and Grisebach, H. Purification and properties of a S-adenosylmethionine: isoflavone 4'-O-methyltransferase from cell suspension cultures of Cicer arietinum L. Eur. J. Biochem. 50 (1974) 135-143. [PMID: 4452353]

EC 2.1.1.231

Accepted name: flavonoid 4'-O-methyltransferase

Reaction: S-adenosyl-L-methionine + a 4'-hydroxyflavanone = S-adenosyl-L-homocysteine + a 4'-methoxyflavanone

For diagram of reaction, click here

Other name(s): SOMT-2; 4'-hydroxyisoflavone methyltransferase

Systematic name: S-adenosyl-L-methionine:flavonoid 4'-O-methyltransferase

Comments: The enzyme catalyses the 4'-methylation of naringenin. In vitro it catalyses the 4'-methylation of apigenin, quercetin, daidzein and genistein.

References:

1. Kim, D.H., Kim, B.G., Lee, Y., Ryu, J.Y., Lim, Y., Hur, H.G. and Ahn, J.H. Regiospecific methylation of naringenin to ponciretin by soybean O-methyltransferase expressed in Escherichia coli. J. Biotechnol. 119 (2005) 155-162. [PMID: 15961179]

EC 2.1.1.232

Accepted name: naringenin 7-O-methyltransferase

Reaction: S-adenosyl-L-methionine + (2S)-naringenin = S-adenosyl-L-homocysteine + (2S)-sakuranetin

For diagram of reaction, click here

Glossary: naringenin = (2S)-5,7,4'-trihydroxyflavanone = (2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
sakuranetin = (2S)-5,4'-dihydroxy-7-methoxyflavanone = (2S)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-2,3-dihydrochromen-4-one

Other name(s): NOMT

Systematic name: S-adenosyl-L-methionine:(2S)-5,7,4'-trihydroxyflavanone 7-O-methyltransferase

Comments: The enzyme is involved in the biosynthesis of the sakuranetin, an inducible defense mechanism of Oryza sativa against pathogen attack.

References:

1. Rakwal, R., Agrawal, G.K., Yonekura, M. and Kodama, O. Naringenin 7-O-methyltransferase involved in the biosynthesis of the flavanone phytoalexin sakuranetin from rice (Oryza sativa L.). Plant Sci. 155 (2000) 213-221. [PMID: 10814825]

EC 2.4.1.276

Accepted name: zeaxanthin glucosyltransferase

Reaction: 2 UDP-glucose + zeaxanthin = 2 UDP + zeaxanthin bis(β-D-glucoside)

For diagram of reaction, click here

Other name(s): crtX (gene name)

Systematic name: UDP-glucose:zeaxanthin β-D-glucosyltransferase

Comments: The reaction proceeds in two steps with the monoglucoside as an intermediate.

References:

1. Hundle, B.S., O'Brien, D.A., Alberti, M., Beyer, P. and Hearst, J.E. Functional expression of zeaxanthin glucosyltransferase from Erwinia herbicola and a proposed uridine diphosphate binding site. Proc. Natl. Acad. Sci. USA 89 (1992) 9321-9325. [PMID: 1409639]

EC 2.5.1.96

Accepted name: 4,4'-diapophytoene synthase

Reaction: 2 (2E,6E)-farnesyl diphosphate = 15-cis-4,4'-diapophytoene + 2 diphosphate (overall reaction)
(1a) 2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate
(1b) presqualene diphosphate = 15-cis-4,4'-diapophytoene + diphosphate

For diagram of reaction, click here

Other name(s): dehydrosqualene synthase; DAP synthase; C₃₀ carotene synthase; CrtM

Systematic name: farnesyl-diphosphate:farnesyl-diphosphate farnesyltransferase (15-cis-4,4'-diapophytoene forming)

Comments: Requires Mn²⁺. Typical of Staphylococcus aureus and some other bacteria such as Heliobacillus sp.

References:

1. Umeno, D., Tobias, A.V. and Arnold, F.H. Evolution of the C₃₀ carotenoid synthase CrtM for function in a C₄₀ pathway. J. Bacteriol. 184 (2002) 6690-6699. [PMID: 12426357]

2. Pelz, A., Wieland, K.P., Putzbach, K., Hentschel, P., Albert, K. and Gotz, F. Structure and biosynthesis of staphyloxanthin from Staphylococcus aureus. J. Biol. Chem. 280 (2005) 32493-32498. [PMID: 16020541]

3. Ku, B., Jeong, J.C., Mijts, B.N., Schmidt-Dannert, C. and Dordick, J.S. Preparation, characterization, and optimization of an in vitro C₃₀ carotenoid pathway. Appl. Environ. Microbiol. 71 (2005) 6578-6583. [PMID: 16269684]

4. Liu, C.I., Liu, G.Y., Song, Y., Yin, F., Hensler, M.E., Jeng, W.Y., Nizet, V., Wang, A.H. and Oldfield, E. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science 319 (2008) 1391-1394. [PMID: 18276850]

*EC 2.7.1.170

Accepted name: anhydro-N-acetylmuramic acid kinase

Reaction: ATP + 1,6-anhydro-N-acetyl-β-muramate + H₂O = ADP + N-acetylmuramate 6-phosphate

Other name(s): anhMurNAc kinase; AnmK

Systematic name: ATP:1,6-anhydro-N-acetyl-β-muramate 6-phosphotransferase

Comments: This enzyme, along with EC 4.2.1.126, N-acetylmuramic acid 6-phosphate etherase, is required for the utilization of anhydro-N-acetylmuramic acid in proteobacteria. The substrate is either imported from the medium or derived from the bacterium's own cell wall murein during cell wall recycling. The product N-acetylmuramate 6-phosphate is produced as a 7:1 mixture of the α- and β-anomers.

Links to other databases: BRENDA, EXPASY, KEGG

References:

1. Uehara, T., Suefuji, K., Valbuena, N., Meehan, B., Donegan, M. and Park, J.T. Recycling of the anhydro-N-acetylmuramic acid derived from cell wall murein involves a two-step conversion to N-acetylglucosamine-phosphate. J. Bacteriol. 187 (2005) 3643-3649. [PMID: 15901686]

2. Uehara, T., Suefuji, K., Jaeger, T., Mayer, C. and Park, J.T. MurQ etherase is required by Escherichia coli in order to metabolize anhydro-N-acetylmuramic acid obtained either from the environment or from its own cell wall. J. Bacteriol. 188 (2006) 1660-1662. [PMID: 16452451]

3. Bacik, J.P., Whitworth, G.E., Stubbs, K.A., Yadav, A.K., Martin, D.R., Bailey-Elkin, B.A., Vocadlo, D.J. and Mark, B.L. Molecular basis of 1,6-anhydro bond cleavage and phosphoryl transfer by Pseudomonas aeruginosa 1,6-anhydro-N-acetylmuramic acid kinase. J. Biol. Chem. 286 (2011) 12283-12291. [PMID: 21288904]

EC 2.8.1.10

Accepted name: thiazole synthase

Reaction: 1-deoxy-D-xylulose 5-phosphate + 2-iminoacetate + thiocarboxy-adenylate-[sulfur-carrier protein ThiS] = 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + [sulfur-carrier protein ThiS] + 2 H₂O

Glossary: cThz*-P = 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate

Other name(s): thiG (gene name)

Systematic name: 1-deoxy-D-xylulose 5-phosphate:thiol sulfurtransferase

Comments: H₂S can provide the sulfur in vitro. Part of the pathway for thiamine biosynthesis.

References:

1. Park, J.H., Dorrestein, P.C., Zhai, H., Kinsland, C., McLafferty, F.W. and Begley, T.P. Biosynthesis of the thiazole moiety of thiamin pyrophosphate (vitamin B₁). Biochemistry 42 (2003) 12430-12438. [PMID: 14567704]

2. Dorrestein, P.C., Zhai, H., McLafferty, F.W. and Begley, T.P. The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiS. Chem. Biol. 11 (2004) 1373-1381. [PMID: 15489164]

3. Dorrestein, P.C., Zhai, H., Taylor, S.V., McLafferty, F.W. and Begley, T.P. The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B₁): the early steps catalyzed by thiazole synthase. J. Am. Chem. Soc. 126 (2004) 3091-3096. [PMID: 15012138]

4. Settembre, E.C., Dorrestein, P.C., Zhai, H., Chatterjee, A., McLafferty, F.W., Begley, T.P. and Ealick, S.E. Thiamin biosynthesis in Bacillus subtilis: structure of the thiazole synthase/sulfur carrier protein complex. Biochemistry 43 (2004) 11647-11657. [PMID: 15362849]

5. Hazra, A., Chatterjee, A. and Begley, T.P. Biosynthesis of the thiamin thiazole in Bacillus subtilis: identification of the product of the thiazole synthase-catalyzed reaction. J. Am. Chem. Soc. 131 (2009) 3225-3229. [PMID: 19216519]

6. Hazra, A.B., Han, Y., Chatterjee, A., Zhang, Y., Lai, R.Y., Ealick, S.E. and Begley, T.P. A missing enzyme in thiamin thiazole biosynthesis: identification of TenI as a thiazole tautomerase. J. Am. Chem. Soc. 133 (2011) 9311-9319. [PMID: 21534620]

*EC 2.8.4.1

Accepted name: coenzyme-B sulfoethylthiotransferase

Reaction: methyl-CoM + CoB = CoM-S-S-CoB + methane

For diagram of reaction click here

Glossary: coenzyme B (CoB) = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate = N-(7-thioheptanoyl)-3-O-phosphothreonine
coenzyme M (CoM) = 2-mercaptoethanesulfonate
2-(methylthio)ethanesulfonate = methyl-CoM

Other name(s): methyl-CoM reductase; methyl coenzyme M reductase

Systematic name: methyl-CoM:CoB S-(2-sulfoethyl)thiotransferase

Comments: This enzyme catalyses the final step in methanogenesis, the biological production of methane. This important anaerobic process is carried out only by methanogenic archaea. The enzyme can also function in reverse, for anaerobic oxidation of methane. The enzyme requires the hydroporphinoid nickel complex coenzyme F₄₃₀. Highly specific for coenzyme B with a heptanoyl chain; ethyl CoM and difluoromethyl CoM are poor substrates. The sulfide sulfur can be replaced by selenium but not by oxygen.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, UM-BBD

References:

1. Bobik, T.A., Olson, K.D., Noll, K.M. and Wolfe, R.S. Evidence that the heterodisulfide of coenzyme-M and 7-mercaptanoylthreonine phosphate is a product of the methylreductase reaction in Methanobacterium. Biochem. Biophys. Res. Commun. 149 (1987) 455-460. [PMID: 3122735]

2. Ellermann, J., Hedderich, R., Boecher, R. and Thauer, R.K. The final step in methane formation: investigations with highly purified methyl coenzyme M reductase component C from Methanobacterium thermoautotrophicum (strain Marburg). Eur. J. Biochem. 184 (1988) 63-68.

3. Ermler, U., Grabarse, W., Shima, S., Goubeaud, M. and Thauer, R.K. Crystal structure of methyl coenzyme M reductase: The key enzyme of biological methane formation. Science 278 (1997) 1457-1462. [PMID: 9367957]

4. Signor, L., Knuppe, C., Hug, R., Schweizer, B., Pfaltz, A. and Jaun, B. Methane formation by reaction of a methyl thioether with a photo-excited nickel thiolate — a process mimicking methanogenesis in Archaea. Chemistry 6 (2000) 3508-3516. [PMID: 11072815]

5. Scheller, S., Goenrich, M., Boecher, R., Thauer, R.K. and Jaun, B. The key nickel enzyme of methanogenesis catalyses the anaerobic oxidation of methane. Nature 465 (2010) 606-608. [PMID: 20520712]

[EC 3.1.1.21 Deleted entry: retinyl-palmitate esterase. Now known to be catalysed by EC 3.1.1.1, carboxylesterase and EC 3.1.1.3, triacylglycerol lipase. (EC 3.1.1.21 created 1972, deleted 2011)]

EC 3.1.4.54

Accepted name: N-acetylphosphatidylethanolamine-hydrolysing phospholipase D

Reaction: N-acylphosphatidylethanolamine + H₂O = N-acylethanolamine + a 1,2-diacylglycerol 3-phosphate

Other name(s): NAPE-PLD; anandamide-generating phospholipase D; N-acyl phosphatidylethanolamine phospholipase D; NAPE-hydrolyzing phospholipase D

Systematic name: N-acetylphosphatidylethanolamine phosphatidohydrolase

Comments: This enzyme is involved in the biosynthesis of anandamide. It does not hydrolyse phosphatidylcholine and phosphatidylethanolamine [1]. No transphosphatidation [1]. The enzyme contains Zn²⁺ and is activated by Mg²⁺ or Ca²⁺ [2].

References:

1. Okamoto, Y., Morishita, J., Tsuboi, K., Tonai, T. and Ueda, N. Molecular characterization of a phospholipase D generating anandamide and its congeners. J. Biol. Chem. 279 (2004) 5298-5305. [PMID: 14634025]

2. Wang, J., Okamoto, Y., Morishita, J., Tsuboi, K., Miyatake, A. and Ueda, N. Functional analysis of the purified anandamide-generating phospholipase D as a member of the metallo-β-lactamase family. J. Biol. Chem. 281 (2006) 12325-12335. [PMID: 16527816]

EC 4.2.1.131

Accepted name: carotenoid 1,2-hydratase

Reaction: (1) 1-hydroxy-1,2-dihydrolycopene = lycopene + H₂O
(2) 1,1'-dihydroxy-1,1',2,2'-tetrahydrolycopene = 1-hydroxy-1,2-dihydrolycopene + H₂O

For diagram of reaction click here or click here

Other name(s): CrtC

Systematic name: lycopene hydro-lyase (1-hydroxy-1,2-dihydrolycopene-forming)

Comments: In Rubrivivax gelatinosus [1] and Thiocapsa roseopersicina [2] both products are formed, whereas Rhodobacter capsulatus [1] only gives 1-hydroxy-1,2-dihydrolycopene. Also acts on neurosporene giving 1-hydroxy-1,2-dihydroneurosporene with both organism but 1,1'-dihydroxy-1,1',2,2'-tetrahydroneurosporene only with Rubrivivax gelatinosus.

References:

1. Steiger, S., Mazet, A. and Sandmann, G. Heterologous expression, purification, and enzymatic characterization of the acyclic carotenoid 1,2-hydratase from Rubrivivax gelatinosus. Arch. Biochem. Biophys. 414 (2003) 51-58. [PMID: 12745254]

2. Hiseni, A., Arends, I.W. and Otten, L.G. Biochemical characterization of the carotenoid 1,2-hydratases (CrtC) from Rubrivivax gelatinosus and Thiocapsa roseopersicina. Appl. Microbiol. Biotechnol. (2011) . [PMID: 21590288]

EC 4.2.3.84

Accepted name: 10-epi-γ-eudesmol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H₂O = 10-epi-γ-eudesmol + diphosphate

For diagram of reaction click here and mechanism click here

Glossary: 10-epi-γ-eudesmol = 2-[(2R,4aS)-4a,8-dimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-yl]propan-2-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (10-epi-γ-eudesmol-forming)

Comments: The recombinant enzyme from ginger (Zingiber zerumbet) gives 62.6% β-eudesmol, 16.8% 10-epi-γ-eudesmol, 10% α-eudesmol, and 5.6% aristolene. cf. EC 4.2.3.68 (β-eudesmol synthase) and EC 4.2.3.85 (α-eudesmol synthase)

References:

1. Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565-572. [PMID: 18242187]

EC 4.2.3.85

Accepted name: α-eudesmol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H₂O = α-eudesmol + diphosphate

For diagram of reaction click here and mechanism click here

Glossary: (–)-α-eudesmol = 2-[(2R,4aR,8aR)-4a,8-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalen-2-yl]propan-2-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-eudesmol-forming)

Comments: The recombinant enzyme from ginger (Zingiber zerumbet) gives 62.6% β-eudesmol, 16.8% 10-epi-γ-eudesmol, 10% α-eudesmol, and 5.6% aristolene. cf. EC 4.2.3.68 (β-eudesmol synthase) and EC 4.2.3.84 (10-epi-γ-eudesmol synthase)

References:

1. Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565-572. [PMID: 18242187]

*EC 5.4.99.25

Accepted name: tRNA pseudouridine⁵⁵ synthase

Reaction: tRNA uridine⁵⁵ = tRNA pseudouridine⁵⁵

Other name(s): TruB; aCbf5; Pus4; YNL292w (gene name); Ψ⁵⁵ tRNA pseudouridine synthase; tRNA:Ψ⁵⁵-synthase; tRNA pseudouridine 55 synthase; tRNA:pseudouridine-55 synthase; Ψ⁵⁵ synthase; tRNA Ψ⁵⁵ synthase; tRNA:Ψ⁵⁵ synthase; tRNA-uridine⁵⁵ uracil mutase; Pus10; tRNA-uridine^54/55 uracil mutase

Systematic name: tRNA-uridine⁵⁵ uracil mutase

Comments: Pseudouridine synthase TruB from Escherichia coli specifically modifies uridine⁵⁵ in tRNA molecules [1]. The bifunctional archaeal enzyme also catalyses the pseudouridylation of uridine⁵⁴ [6]. It is not known whether the enzyme from Escherichia coli can also act on position 54 in vitro, since this position is occupied in Escherichia coli tRNAs by thymine.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 430429-15-5

References:

1. Nurse, K., Wrzesinski, J., Bakin, A., Lane, B.G. and Ofengand, J. Purification, cloning, and properties of the tRNA Ψ55 synthase from Escherichia coli. RNA 1 (1995) 102-112. [PMID: 7489483]

2. Becker, H.F., Motorin, Y., Planta, R.J. and Grosjean, H. The yeast gene YNL292w encodes a pseudouridine synthase (Pus4) catalyzing the formation of Ψ55 in both mitochondrial and cytoplasmic tRNAs. Nucleic Acids Res. 25 (1997) 4493-4499. [PMID: 9358157]

3. Pienkowska, J., Wrzesinski, J. and Szweykowska-Kulinska, Z. A cell-free yellow lupin extract containing activities of pseudouridine 35 and 55 synthases. Acta Biochim. Pol. 45 (1998) 745-754. [PMID: 9918501]

4. Chaudhuri, B.N., Chan, S., Perry, L.J. and Yeates, T.O. Crystal structure of the apo forms of Ψ55 tRNA pseudouridine synthase from Mycobacterium tuberculosis: a hinge at the base of the catalytic cleft. J. Biol. Chem. 279 (2004) 24585-24591. [PMID: 15028724]

5. Hoang, C., Hamilton, C.S., Mueller, E.G. and Ferre-D'Amare, A.R. Precursor complex structure of pseudouridine synthase TruB suggests coupling of active site perturbations to an RNA-sequestering peripheral protein domain. Protein Sci. 14 (2005) 2201-2206. [PMID: 15987897]

6. Gurha, P. and Gupta, R. Archaeal Pus10 proteins can produce both pseudouridine 54 and 55 in tRNA. RNA 14 (2008) 2521-2527. [PMID: 18952823]

EC 5.4.99.45

Accepted name: tRNA pseudouridine^38/39 synthase

Reaction: tRNA uridine^38/39 = tRNA pseudouridine^38/39

Other name(s): Deg1; Pus3p; pseudouridine synthase 3

Systematic name: tRNA-uridine^38/39 uracil mutase

Comments: The enzyme from Saccharomyces cerevisiae is active only towards uridine³⁸ and uridine³⁹, and shows no activity with uridine⁴⁰ (cf. EC 5.4.99.12, tRNA pseudouridine^38-40 synthase) [1]. In vitro the enzyme from mouse is active on uridine³⁹ and very slightly on uridine³⁸ (human tRNA^Leu) [2].

References:

1. Lecointe, F., Simos, G., Sauer, A., Hurt, E.C., Motorin, Y. and Grosjean, H. Characterization of yeast protein Deg1 as pseudouridine synthase (Pus3) catalyzing the formation of Ψ³⁸ and Ψ³⁹ in tRNA anticodon loop. J. Biol. Chem. 273 (1998) 1316-1323. [PMID: 9430663]

2. Chen, J. and Patton, J.R. Pseudouridine synthase 3 from mouse modifies the anticodon loop of tRNA. Biochemistry 39 (2000) 12723-12730. [PMID: 11027153]