Proposed Changes to the Enzyme List

References:

1.	Edenharder, R., Pfutzner, A. and Hammann, R. Characterization of NAD-dependent 3 α- and 3 β-hydroxysteroid dehydrogenase and of NADP-dependent 7 β-hydroxysteroid dehydrogenase from Peptostreptococcus productus. Biochim. Biophys. Acta 1004 (1989) 230–238. [DOI] [PMID: 2752021]
2.	Edenharder, R. and Pfutzner, M. Partial purification and characterization of an NAD-dependent 3 β-hydroxysteroid dehydrogenase from Clostridium innocuum. Appl. Environ. Microbiol. 55 (1989) 1656–1659. [PMID: 2764572]
3.	Devlin, A.S. and Fischbach, M.A. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 11 (2015) 685–690. [DOI] [PMID: 26192599]

[EC 1.1.1.391 created 2016]

1.1.1.392

Accepted name:

3α-hydroxycholanate dehydrogenase (NADP⁺)

Reaction:

lithocholate + NADP⁺ = 3-oxo-5β-cholan-24-oate + NADPH + H⁺

Glossary:

lithocholate = 3α-hydroxy-5β-cholan-24-oate

Other name(s):

α-hydroxy-cholanate dehydrogenase (ambiguous)

Systematic name:

lithocholate:NADP⁺ 3-oxidoreductase

Comments:

This bacterial enzyme is involved in the modification of secondary bile acids to form 3β-bile acids (also known as iso-bile acids) via a 3-oxo intermediate. The enzyme catalyses a reversible reaction in vitro. Also acts on related bile acids. cf. EC 1.1.1.52, 3α-hydroxycholanate dehydrogenase (NAD⁺).

Links to other databases:

BRENDA, EXPASY, KEGG, CAS registry number: 9028-57-3

References:

1.	Devlin, A.S. and Fischbach, M.A. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 11 (2015) 685–690. [DOI] [PMID: 26192599]

[EC 1.1.1.392 created 2016]

1.1.1.393

Accepted name:

3β-hydroxycholanate 3-dehydrogenase (NADP⁺)

Reaction:

isolithocholate + NADP⁺ = 3-oxo-5β-cholan-24-oate + NADPH + H⁺

Glossary:

isolithocholate = 3β-hydroxy-5β-cholan-24-oate

Other name(s):

3β-hydroxysteroid dehydrogenase (ambiguous)

Systematic name:

isolithocholate:NADP⁺ 3-oxidoreductase

Comments:

Links to other databases:

References:

1.	Akao, T., Akao, T., Hattori, M., Namba, T. and Kobashi, K. 3 β-Hydroxysteroid dehydrogenase of Ruminococcus sp. from human intestinal bacteria. J. Biochem. 99 (1986) 1425–1431. [PMID: 3458705]
2.	Devlin, A.S. and Fischbach, M.A. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 11 (2015) 685–690. [DOI] [PMID: 26192599]

[EC 1.1.1.393 created 2016]

1.1.1.394

Accepted name:

aurachin B dehydrogenase

Reaction:

aurachin B + NAD⁺ + H₂O = 4-[(2E,6E)-farnesyl]-4-hydroxy-2-methyl-3-oxo-3,4-dihydroquinoline 1-oxide + NADH + H⁺ (overall reaction)
(1a) 4-[(2E,6E)-farnesyl]-3,4-dihydroxy-2-methyl-3,4-dihydroquinoline 1-oxide + NAD⁺ = 4-[(2E,6E)-farnesyl]-4-hydroxy-2-methyl-3-oxo-3,4-dihydroquinoline 1-oxide + NADH + H⁺
(1b) aurachin B + H₂O = 4-[(2E,6E)-farnesyl]-3,4-dihydroxy-2-methyl-3,4-dihydroquinoline 1-oxide (spontaneous)

For diagram of aurachine biosynthesis, click here

Glossary:

aurachin B= 4-[(2E,6E,10E)-3,7-dimethyldodeca-2,6,10-trien-1-yl]-3-hydroxy-2-methylquinoline 1-oxide

Other name(s):

AuaH

Systematic name:

aurachin B:NAD⁺ 3-oxidoreductase

Comments:

The enzyme from the bacterium Stigmatella aurantiaca catalyses the final step in the conversion of aurachin C to aurachin B. In vivo the enzyme catalyses the reduction of 4-[(2E,6E)-farnesyl]-4-hydroxy-2-methyl-3-oxo-3,4-dihydroquinoline-1-oxide to form 4-[(2E,6E)-farnesyl]-2-methyl-1-oxo-3,4-dihydroquinoline-3,4-diol (note that the reactions written above proceed from right to left), which then undergoes a spontaneous dehydration to form aurachin B.

Links to other databases:

References:

1.	Katsuyama, Y., Harmrolfs, K., Pistorius, D., Li, Y. and Muller, R. A semipinacol rearrangement directed by an enzymatic system featuring dual-function FAD-dependent monooxygenase. Angew. Chem. Int. Ed. Engl. 51 (2012) 9437–9440. [DOI] [PMID: 22907798]

[EC 1.1.1.394 created 2016]

1.2.5.3

Accepted name:

aerobic carbon monoxide dehydrogenase

Reaction:

CO + a quinone + H₂O = CO₂ + a quinol

Other name(s):

MoCu-CODH; coxSML (gene names); molybdoenzyme carbon monoxide dehydrogenase

Systematic name:

carbon-monoxide,water:quinone oxidoreductase

Comments:

This enzyme, found in carboxydotrophic bacteria, catalyses the oxidation of CO to CO₂ under aerobic conditions. The enzyme contains a binuclear Mo-Cu cluster in which the copper is ligated to a molybdopterin center via a sulfur bridge. The enzyme also contains two [2Fe-2S] clusters and FAD, and belongs to the xanthine oxidoreductase family. The CO₂ that is produced is assimilated by the Calvin-Benson-Basham cycle, while the electrons are transferred to a quinone via the FAD site, and continue through the electron transfer chain to a dioxygen terminal acceptor [5]. cf. EC 1.2.7.4, anaerobic carbon monoxide dehydrogenase.

Links to other databases:

References:

1.	Gremer, L., Kellner, S., Dobbek, H., Huber, R. and Meyer, O. Binding of flavin adenine dinucleotide to molybdenum-containing carbon monoxide dehydrogenase from Oligotropha carboxidovorans. Structural and functional analysis of a carbon monoxide dehydrogenase species in which the native flavoprotein has been replaced by its recombinant counterpart produced in Escherichia coli. J. Biol. Chem. 275 (2000) 1864–1872. [DOI] [PMID: 10636886]
2.	Dobbek, H., Gremer, L., Kiefersauer, R., Huber, R. and Meyer, O. Catalysis at a dinuclear [CuSMo(==O)OH] cluster in a CO dehydrogenase resolved at 1.1-Å resolution. Proc. Natl. Acad. Sci. USA 99 (2002) 15971–15976. [DOI] [PMID: 12475995]
3.	Gnida, M., Ferner, R., Gremer, L., Meyer, O. and Meyer-Klaucke, W. A novel binuclear [CuSMo] cluster at the active site of carbon monoxide dehydrogenase: characterization by X-ray absorption spectroscopy. Biochemistry 42 (2003) 222–230. [DOI] [PMID: 12515558]
4.	Resch, M., Dobbek, H. and Meyer, O. Structural and functional reconstruction in situ of the [CuSMoO₂] active site of carbon monoxide dehydrogenase from the carbon monoxide oxidizing eubacterium Oligotropha carboxidovorans. J. Biol. Inorg. Chem. 10 (2005) 518–528. [DOI] [PMID: 16091936]
5.	Wilcoxen, J., Zhang, B. and Hille, R. Reaction of the molybdenum- and copper-containing carbon monoxide dehydrogenase from Oligotropha carboxidovorans with quinones. Biochemistry 50 (2011) 1910–1916. [DOI] [PMID: 21275368]
6.	Pelzmann, A.M., Mickoleit, F. and Meyer, O. Insights into the posttranslational assembly of the Mo-, S- and Cu-containing cluster in the active site of CO dehydrogenase of Oligotropha carboxidovorans. J. Biol. Inorg. Chem. 19 (2014) 1399–1414. [DOI] [PMID: 25377894]
7.	Hille, R., Dingwall, S. and Wilcoxen, J. The aerobic CO dehydrogenase from Oligotropha carboxidovorans. J. Biol. Inorg. Chem. 20 (2015) 243–251. [DOI] [PMID: 25156151]

[EC 1.2.5.3 created 2016]

*EC

1.2.7.4

Accepted name:

anaerobic carbon monoxide dehydrogenase

Reaction:

CO + H₂O + 2 oxidized ferredoxin = CO₂ + 2 reduced ferredoxin + 2 H⁺

Other name(s):

Ni-CODH; carbon-monoxide dehydrogenase (ferredoxin)

Systematic name:

carbon-monoxide,water:ferredoxin oxidoreductase

Comments:

This prokaryotic enzyme catalyses the reversible reduction of CO₂ to CO. The electrons are transferred to redox proteins such as ferredoxin. In purple sulfur bacteria and methanogenic archaea it catalyses the oxidation of CO to CO₂, which is incorporated by the Calvin-Benson-Basham cycle or released, respectively. In acetogenic and sulfate-reducing microbes it catalyses the reduction of CO₂ to CO, which is incorporated into acetyl CoA by EC 2.3.1.169, CO-methylating acetyl-CoA synthase, with which the enzyme forms a tight complex in those organisms. The enzyme contains five metal clusters per homodimeric enzyme: two nickel-iron-sulfur clusters called the C-Clusters, one [4Fe-4S] D-cluster; and two [4Fe-4S] B-clusters. In methanogenic archaea additional [4Fe-4S] clusters exist, presumably as part of the electron transfer chain. In purple sulfur bacteria the enzyme forms complexes with the Ni-Fe-S protein EC 1.12.7.2, ferredoxin hydrogenase, which catalyse the overall reaction: CO + H₂O = CO₂ + H₂. cf. EC 1.2.5.3, aerobic carbon monoxide dehydrogenase.

Links to other databases:

References:

1.	Ragsdale, S.W., Clark, J.E., Ljungdahl, L.G., Lundie, L.L. and Drake, H.L. Properties of purified carbon monoxide dehydrogenase from Clostridium thermoaceticum, a nickel, iron-sulfur protein. J. Biol. Chem. 258 (1983) 2364–2369. [PMID: 6687389]
2.	Diekert, G. and Ritter, M. Purification of the nickel protein carbon monoxide dehydrogenase of Clostridium thermoaceticum. FEBS Lett. 151 (1983) 41–44. [DOI] [PMID: 6687458]
3.	Bonam, D. and Ludden, P.W. Purification and characterization of carbon monoxide dehydrogenase, a nickel, zinc, iron-sulfur protein, from Rhodospirillum rubrum. J. Biol. Chem. 262 (1987) 2980–2987. [PMID: 3029096]
4.	Drennan, C.L., Heo, J., Sintchak, M.D., Schreiter, E. and Ludden, P.W. Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase. Proc. Natl. Acad. Sci. USA 98 (2001) 11973–11978. [DOI] [PMID: 11593006]
5.	Dobbek, H., Svetlitchnyi, V., Gremer, L., Huber, R. and Meyer, O. Crystal structure of a carbon monoxide dehydrogenase reveals a [Ni-4Fe-5S] cluster. Science 293 (2001) 1281–1285. [DOI] [PMID: 11509720]
6.	Doukov, T.I., Iverson, T., Seravalli, J., Ragsdale, S.W. and Drennan, C.L. A Ni-Fe-Cu center in a bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase. Science 298 (2002) 567–572. [DOI] [PMID: 12386327]
7.	Can, M., Armstrong, F.A. and Ragsdale, S.W. Structure, function, and mechanism of the nickel metalloenzymes, CO dehydrogenase, and acetyl-CoA synthase. Chem. Rev. 114 (2014) 4149–4174. [DOI] [PMID: 24521136]

[EC 1.2.7.4 created 2003 (EC 1.2.99.2 created 1982, modified 1990, modified 2003, incorporated 2015), modified 2016]

1.2.99.2

Transferred entry:

carbon-monoxide dehydrogenase (acceptor). Now EC 1.2.7.4, carbon-monoxide dehydrogenase (ferredoxin)

[EC 1.2.99.2 created 1982, modified 1990, modified 2003, deleted 2016]

1.3.1.80

Transferred entry:

red chlorophyll catabolite reductase. Now classified as EC 1.3.7.12, red chlorophyll catabolite reductase

[EC 1.3.1.80 created 2007, deleted 2016]

1.3.1.111

Accepted name:

geranylgeranyl-bacteriochlorophyllide a reductase

Reaction:

bacteriochlorophyll a + 3 NADP⁺ = geranylgeranyl bacteriochlorophyllide a + 3 NADPH + 3 H⁺

For diagram of bacteriochlorophyl a biosynthesis, click here

Other name(s):

geranylgeranyl-bacteriopheophytin reductase; bchP (gene name)

Systematic name:

bacteriochlorophyll-a:NADP⁺ oxidoreductase (geranylgeranyl-reducing)

Comments:

The enzyme catalyses the successive reduction of the geranylgeraniol esterifying group to phytol, reducing three out of four double bonds, and transforming geranylgeranyl bacteriochlorophyllide a via dihydrogeranylgeranyl bacteriochlorophyllide a and tetrahydrogeranylgeranyl bacteriochlorophyllide a to bacteriochlorophyll a. The enzyme can also accept the pheophytin derivative geranylgeranyl bacteriopheophytin, converting it to bacteriopheophytin a.

Links to other databases:

References:

1.	Bollivar, D.W., Wang, S., Allen, J.P. and Bauer, C.E. Molecular genetic analysis of terminal steps in bacteriochlorophyll a biosynthesis: characterization of a Rhodobacter capsulatus strain that synthesizes geranylgeraniol-esterified bacteriochlorophyll a. Biochemistry 33 (1994) 12763–12768. [PMID: 7947681]
2.	Addlesee, H.A. and Hunter, C.N. Physical mapping and functional assignment of the geranylgeranyl-bacteriochlorophyll reductase gene, bchP, of Rhodobacter sphaeroides. J. Bacteriol. 181 (1999) 7248–7255. [PMID: 10572128]
3.	Addlesee, H.A. and Hunter, C.N. Rhodospirillum rubrum possesses a variant of the bchP gene, encoding geranylgeranyl-bacteriopheophytin reductase. J. Bacteriol. 184 (2002) 1578–1586. [DOI] [PMID: 11872709]
4.	Harada, J., Miyago, S., Mizoguchi, T., Azai, C., Inoue, K., Tamiaki, H. and Oh-oka, H. Accumulation of chlorophyllous pigments esterified with the geranylgeranyl group and photosynthetic competence in the CT2256-deleted mutant of the green sulfur bacterium Chlorobium tepidum. Photochem Photobiol Sci 7 (2008) 1179–1187. [DOI] [PMID: 18846281]

[EC 1.3.1.111 created 2016]

1.3.7.12

Accepted name:

red chlorophyll catabolite reductase

Reaction:

primary fluorescent chlorophyll catabolite + 2 oxidized ferredoxin [iron-sulfur] cluster = red chlorophyll catabolite + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺

For diagram of chlorophyll catabolism, click here

Glossary:

red chlorophyll catabolite = RCC = (7S,8S,10¹R)-8-(2-carboxyethyl)-17-ethyl-19-formyl-10¹-(methoxycarbonyl)-3,7,13,18-tetramethyl-2-vinyl-8,23-dihydro-7H-10,12-ethanobiladiene-ab-1,10²(21H)-dione
primary fluorescent chlorophyll catabolite = pFCC = (8²R,12S,13S)-12-(2-carboxyethyl)-3-ethyl-1-formyl-8²-(methoxycarbonyl)-2,7,13,17-tetramethyl-18-vinyl-12,13-dihydro-8,10-ethanobilene-b-8¹,19(16H)-dione

Other name(s):

RCCR; RCC reductase; red Chl catabolite reductase

Systematic name:

primary fluorescent chlorophyll catabolite:ferredoxin oxidoreductase

Comments:

The enzyme participates in chlorophyll degradation, which occurs during leaf senescence and fruit ripening in higher plants. The reaction requires reduced ferredoxin, which is generated from NADPH produced either through the pentose-phosphate pathway or by the action of photosystem I [1,2]. This reaction takes place while red chlorophyll catabolite is still bound to EC 1.14.15.17, pheophorbide a oxygenase [3]. Depending on the plant species used as the source of enzyme, one of two possible C-1 epimers of primary fluorescent chlorophyll catabolite (pFCC), pFCC-1 or pFCC-2, is normally formed, with all genera or species within a family producing the same isomer [3,4]. After modification and export, pFCCs are eventually imported into the vacuole, where the acidic environment causes their non-enzymic conversion into colourless breakdown products called non-fluorescent chlorophyll catabolites (NCCs) [2].

Links to other databases:

References:

1.	Rodoni, S., Mühlecker, W., Anderl, M., Kräutler, B., Moser, D., Thomas, H., Matile, P. and Hörtensteiner, S. Chlorophyll breakdown in senescent chloroplasts. Cleavage of pheophorbide a in two enzymic steps. Plant Physiol. 115 (1997) 669–676. [PMID: 12223835]
2.	Wüthrich, K.L., Bovet, L., Hunziker, P.E., Donnison, I.S. and Hörtensteiner, S. Molecular cloning, functional expression and characterisation of RCC reductase involved in chlorophyll catabolism. Plant J. 21 (2000) 189–198. [DOI] [PMID: 10743659]
3.	Pružinská, A., Anders, I., Aubry, S., Schenk, N., Tapernoux-Lüthi, E., Müller, T., Kräutler, B. and Hörtensteiner, S. In vivo participation of red chlorophyll catabolite reductase in chlorophyll breakdown. Plant Cell 19 (2007) 369–387. [DOI] [PMID: 17237353]
4.	Hörtensteiner, S. Chlorophyll degradation during senescence. Annu. Rev. Plant Biol. 57 (2006) 55–77. [DOI] [PMID: 16669755]
5.	Rodoni, S., Vicentini, F., Schellenberg, M., Matile, P. and Hörtensteiner, S. Partial purification and characterization of red chlorophyll catabolite reductase, a stroma protein involved in chlorophyll breakdown. Plant Physiol. 115 (1997) 677–682. [PMID: 12223836]

[EC 1.3.7.12 created 2007 as EC 1.3.1.80, transferred 2016 to EC 1.3.7.12]

*EC

1.11.1.14

Accepted name:

lignin peroxidase

Reaction:

(1) 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol + H₂O₂ = 3,4-dimethoxybenzaldehyde + 2-methoxyphenol + glycolaldehyde + H₂O
(2) 2 (3,4-dimethoxyphenyl)methanol + H₂O₂ = 2 (3,4-dimethoxyphenyl)methanol radical + 2 H₂O

Glossary:

veratryl alcohol = (3,4-dimethoxyphenyl)methanol
veratraldehyde = 3,4-dimethoxybenzaldehyde
2-methoxyphenol = guaiacol

Other name(s):

diarylpropane oxygenase; ligninase I; diarylpropane peroxidase; LiP; diarylpropane:oxygen,hydrogen-peroxide oxidoreductase (C-C-bond-cleaving); 1,2-bis(3,4-dimethoxyphenyl)propane-1,3-diol:hydrogen-peroxide oxidoreductase (incorrect); (3,4-dimethoxyphenyl)methanol:hydrogen-peroxide oxidoreductase

Systematic name:

1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol:hydrogen-peroxide oxidoreductase

Comments:

A hemoprotein, involved in the oxidative breakdown of lignin by white-rot basidiomycete fungi. The reaction involves an initial oxidation of the heme iron by hydrogen peroxide, forming compound I (Fe^IV=O radical cation) at the active site. A single one-electron reduction of compound I by an electron derived from a substrate molecule yields compound II (Fe^IV=O non-radical cation), followed by a second one-electron transfer that returns the enzyme to the ferric oxidation state. The electron transfer events convert the substrate molecule into a transient cation radical intermediate that fragments spontaneously. The enzyme can act on a wide range of aromatic compounds, including methoxybenzenes and nonphenolic β-O-4 linked arylglycerol β-aryl ethers, but cannot act directly on the lignin molecule, which is too large to fit into the active site. However larger lignin molecules can be degraded in the presence of veratryl alcohol. It has been suggested that the free radical that is formed when the enzyme acts on veratryl alcohol can diffuse into the lignified cell wall, where it oxidizes lignin and other organic substrates. In the presence of high concentration of hydrogen peroxide and lack of substrate, the enzyme forms a catalytically inactive form (compound III). This form can be rescued by interaction with two molecules of the free radical products. In the case of veratryl alcohol, such an interaction yields two molecules of veratryl aldehyde.

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, KEGG, PDB, CAS registry number: 93792-13-3

References:

1.	Kersten, P.J., Tien, M., Kalyanaraman, B. and Kirk, T.K. The ligninase of Phanerochaete chrysosporium generates cation radicals from methoxybenzenes. J. Biol. Chem. 260 (1985) 2609–2612. [PMID: 2982828]
2.	Paszczynski, A., Huynh, V.-B. and Crawford, R. Comparison of ligninase-I and peroxidase-M2 from the white-rot fungus Phanerochaete chrysosporium. Arch. Biochem. Biophys. 244 (1986) 750–765. [DOI] [PMID: 3080953]
3.	Harvey, P.J., Schoemaker, H.E. and Palmer, J.M. Veratryl alcohol as a mediator and the role of radical cations in lignin biodegradation by Phanerochaete chrysosporium. FEBS Lett. 195 (1986) 242–246.
4.	Wariishi, H., Marquez, L., Dunford, H.B. and Gold, M.H. Lignin peroxidase compounds II and III. Spectral and kinetic characterization of reactions with peroxides. J. Biol. Chem. 265 (1990) 11137–11142. [PMID: 2162833]
5.	Cai, D.Y. and Tien, M. Characterization of the oxycomplex of lignin peroxidases from Phanerochaete chrysosporium: equilibrium and kinetics studies. Biochemistry 29 (1990) 2085–2091. [PMID: 2328240]
6.	Khindaria, A., Yamazaki, I. and Aust, S.D. Veratryl alcohol oxidation by lignin peroxidase. Biochemistry 34 (1995) 16860–16869. [PMID: 8527462]
7.	Khindaria, A., Yamazaki, I. and Aust, S.D. Stabilization of the veratryl alcohol cation radical by lignin peroxidase. Biochemistry 35 (1996) 6418–6424. [DOI] [PMID: 8639588]
8.	Khindaria, A., Nie, G. and Aust, S.D. Detection and characterization of the lignin peroxidase compound II-veratryl alcohol cation radical complex. Biochemistry 36 (1997) 14181–14185. [DOI] [PMID: 9369491]
9.	Doyle, W.A., Blodig, W., Veitch, N.C., Piontek, K. and Smith, A.T. Two substrate interaction sites in lignin peroxidase revealed by site-directed mutagenesis. Biochemistry 37 (1998) 15097–15105. [DOI] [PMID: 9790672]
10.	Pollegioni, L., Tonin, F. and Rosini, E. Lignin-degrading enzymes. FEBS J. 282 (2015) 1190–1213. [DOI] [PMID: 25649492]

[EC 1.11.1.14 created 1992, modified 2006, modified 2011, modified 2016]

*EC

1.11.1.16

Accepted name:

versatile peroxidase

Reaction:

(1) 1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol + H₂O₂ = 4-hydroxy-3-methoxybenzaldehyde + 2-methoxyphenol + glycolaldehyde + H₂O
(2) 2 manganese(II) + 2 H⁺ + H₂O₂ = 2 manganese(III) + 2 H₂O

Glossary:

4-hydroxy-3-methoxybenzaldehyde = vanillin
2-methoxyphenol = guaiacol

Other name(s):

VP; hybrid peroxidase; polyvalent peroxidase; reactive-black-5:hydrogen-peroxide oxidoreductase

Systematic name:

1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol:hydrogen-peroxide oxidoreductase

Comments:

A hemoprotein. This ligninolytic peroxidase combines the substrate-specificity characteristics of the two other ligninolytic peroxidases, EC 1.11.1.13, manganese peroxidase and EC 1.11.1.14, lignin peroxidase. Unlike these two enzymes, it is also able to oxidize phenols, hydroquinones and both low- and high-redox-potential dyes, due to a hybrid molecular architecture that involves multiple binding sites for substrates [2,4].

Links to other databases:

BRENDA, EXPASY, KEGG, PDB, CAS registry number: 42613-30-9, 114995-15-2

References:

1.	Martínez, M.J., Ruiz-Dueñas, F.J., Guillén, F. and Martínez, A.T. Purification and catalytic properties of two manganese peroxidase isoenzymes from Pleurotus eryngii. Eur. J. Biochem. 237 (1996) 424–432. [DOI] [PMID: 8647081]
2.	Heinfling, A., Ruiz-Dueñas, F.J., Martínez, M.J., Bergbauer, M., Szewzyk, U. and Martínez, A.T. A study on reducing substrates of manganese-oxidizing peroxidases from Pleurotus eryngii and Bjerkandera adusta. FEBS Lett. 428 (1998) 141–146. [DOI] [PMID: 9654123]
3.	Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Molecular characterization of a novel peroxidase isolated from the ligninolytic fungus Pleurotus eryngii. Mol. Microbiol. 31 (1999) 223–235. [DOI] [PMID: 9987124]
4.	Camarero, S., Sarkar, S., Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Description of a versatile peroxidase involved in the natural degradation of lignin that has both manganese peroxidase and lignin peroxidase substrate interaction sites. J. Biol. Chem. 274 (1999) 10324–10330. [DOI] [PMID: 10187820]
5.	Ruiz-Dueñas, F.J., Martínez, M.J. and Martínez, A.T. Heterologous expression of Pleurotus eryngii peroxidase confirms its ability to oxidize Mn²⁺ and different aromatic substrates. Appl. Environ. Microbiol. 65 (1999) 4705–4707. [PMID: 10508113]
6.	Camarero, S., Ruiz-Dueñas, F.J., Sarkar, S., Martínez, M.J. and Martínez, A.T. The cloning of a new peroxidase found in lignocellulose cultures of Pleurotus eryngii and sequence comparison with other fungal peroxidases. FEMS Microbiol. Lett. 191 (2000) 37–43. [DOI] [PMID: 11004397]
7.	Ruiz-Dueñas, F.J., Camarero, S., Pérez-Boada, M., Martínez, M.J. and Martínez, A.T. A new versatile peroxidase from Pleurotus. Biochem. Soc. Trans. 29 (2001) 116–122. [PMID: 11356138]
8.	Banci, L., Camarero, S., Martínez, A.T., Martínez, M.J., Pérez-Boada, M., Pierattelli, R. and Ruiz-Dueñas, F.J. NMR study of manganese(II) binding by a new versatile peroxidase from the white-rot fungus Pleurotus eryngii. J. Biol. Inorg. Chem. 8 (2003) 751–760. [DOI] [PMID: 12884090]
9.	Pérez-Boada, M., Ruiz-Dueñas, F.J., Pogni, R., Basosi, R., Choinowski, T., Martínez, M.J., Piontek, K. and Martínez, A.T. Versatile peroxidase oxidation of high redox potential aromatic compounds: site-directed mutagenesis, spectroscopic and crystallographic investigation of three long-range electron transfer pathways. J. Mol. Biol. 354 (2005) 385–402. [DOI] [PMID: 16246366]
10.	Caramelo, L., Martínez, M.J. and Martínez, A.T. A search for ligninolytic peroxidases in the fungus Pleurotus eryngii involving α-keto-γ-thiomethylbutyric acid and lignin model dimer. Appl. Environ. Microbiol. 65 (1999) 916–922. [PMID: 10049842]

[EC 1.11.1.16 created 2006, modified 2016]

*EC

1.13.11.63

Accepted name:

β-carotene 15,15′-dioxygenase

Reaction:

β-carotene + O₂ = 2 all-trans-retinal

For diagram of retinal and derivatives biosynthesis, click here

Other name(s):

blh (gene name); BCO1 (gene name); BCDO (gene name); carotene dioxygenase; carotene 15,15′-dioxygenase; BCMO1 (misleading); β-carotene 15,15′-monooxygenase (incorrect)

Systematic name:

β-carotene:oxygen 15,15′-dioxygenase (bond-cleaving)

Comments:

Requires Fe²⁺. The enzyme cleaves β-carotene symmetrically, producing two molecules of all-trans-retinal. Both atoms of the oxygen molecule are incorporated into the products [8]. The enzyme can also process β-cryptoxanthin, 8′-apo-β-carotenal, 4′-apo-β-carotenal, α-carotene and γ-carotene in decreasing order. The presence of at least one unsubstituted β-ionone ring in a substrate greater than C₃₀ is mandatory [5]. A prokaryotic enzyme has been reported from the uncultured marine bacterium 66A03, where it is involved in the proteorhodopsin system, which uses retinal as its chromophore [6,7].

Links to other databases:

References:

1.	Goodman, D.S., Huang, H.S. and Shiratori, T. Mechanism of the biosynthesis of vitamin A from β-carotene. J. Biol. Chem. 241 (1966) 1929–1932. [PMID: 5946623]
2.	Goodman, D.S., Huang, H.S., Kanai, M. and Shiratori, T. The enzymatic conversion of all-trans β-carotene into retinal. J. Biol. Chem. 242 (1967) 3543–3554.
3.	Yan, W., Jang, G.F., Haeseleer, F., Esumi, N., Chang, J., Kerrigan, M., Campochiaro, M., Campochiaro, P., Palczewski, K. and Zack, D.J. Cloning and characterization of a human β,β-carotene-15,15′-dioxygenase that is highly expressed in the retinal pigment epithelium. Genomics 72 (2001) 193–202. [DOI] [PMID: 11401432]
4.	Leuenberger, M.G., Engeloch-Jarret, C. and Woggon, W.D. The reaction mechanism of the enzyme-catalysed central cleavage of β-carotene to retinal. Angew. Chem. 40 (2001) 2614–2616. [DOI] [PMID: 11458349]
5.	Kim, Y.S. and Oh, D.K. Substrate specificity of a recombinant chicken β-carotene 15,15′-monooxygenase that converts β-carotene into retinal. Biotechnol. Lett. 31 (2009) 403–408. [DOI] [PMID: 18979213]
6.	Kim, Y.S., Kim, N.H., Yeom, S.J., Kim, S.W. and Oh, D.K. In vitro characterization of a recombinant Blh protein from an uncultured marine bacterium as a β-carotene 15,15′-dioxygenase. J. Biol. Chem. 284 (2009) 15781–15793. [DOI] [PMID: 19366683]
7.	Kim, Y.S., Park, C.S. and Oh, D.K. Retinal production from β-carotene by β-carotene 15,15′-dioxygenase from an unculturable marine bacterium. Biotechnol. Lett. 32 (2010) 957–961. [DOI] [PMID: 20229064]
8.	dela Seña, C., Riedl, K.M., Narayanasamy, S., Curley, R.W., Jr., Schwartz, S.J. and Harrison, E.H. The human enzyme that converts dietary provitamin A carotenoids to vitamin A is a dioxygenase. J. Biol. Chem. 289 (2014) 13661–13666. [DOI] [PMID: 24668807]

[EC 1.13.11.63 created 2012 (EC 1.14.99.36 created 1972 as EC 1.13.11.21, transferred 2001 to EC 1.14.99.36, incorporated 2015), modified 2016]

1.14.11.50

Transferred entry:

(–)-deoxypodophyllotoxin synthase. Now EC 1.14.20.8, (–)-deoxypodophyllotoxin synthase

[EC 1.14.11.50 created 2016, deleted 2018]

1.14.12.20

Transferred entry:

pheophorbide a oxygenase. Now classified as EC 1.14.15.17, pheophorbide a oxygenase.

[EC 1.14.12.20 created 2007, deleted 2016]

*EC

1.14.13.7

Accepted name:

phenol 2-monooxygenase (NADPH)

Reaction:

phenol + NADPH + H⁺ + O₂ = catechol + NADP⁺ + H₂O

For diagram of catechol biosynthesis, click here

Glossary:

o-cresol = 2-cresol = 2-methylphenol

Other name(s):

phenol hydroxylase; phenol o-hydroxylase

Systematic name:

phenol,NADPH:oxygen oxidoreductase (2-hydroxylating)

Comments:

A flavoprotein (FAD). The enzyme from the fungus Trichosporon cutaneum has a broad substrate specificity, and has been reported to catalyse the hydroxylation of a variety of substituted phenols, such as fluoro-, chloro-, amino- and methyl-phenols and also dihydroxybenzenes. cf. EC 1.14.14.20, phenol 2-monooxygenase (FADH₂).

Links to other databases:

BRENDA, EAWAG-BBD, EXPASY, Gene, KEGG, PDB, CAS registry number: 37256-84-1

References:

1.	Nakagawa, H. and Takeda, Y. Phenol hydroxylase. Biochim. Biophys. Acta 62 (1962) 423–426. [DOI] [PMID: 14478080]
2.	Neujahr, H.Y. and Gaal, A. Phenol hydroxylase from yeast. Purification and properties of the enzyme from Trichosporon cutaneum. Eur. J. Biochem. 35 (1973) 386–400. [DOI] [PMID: 4146224]
3.	Neujahr, H.Y. and Gaal, A. Phenol hydroxylase from yeast. Sulfhydryl groups in phenol hydroxylase from Trichosporon cutaneum. Eur. J. Biochem. 58 (1975) 351–357. [DOI] [PMID: 810352]

[EC 1.14.13.7 created 1972, modified 2011, modified 2016]

1.14.13.15

Transferred entry:

cholestanetriol 26-monooxygenase. Now EC 1.14.15.15, cholestanetriol 26-monooxygenase.

[EC 1.14.13.15 created 1976, modified 2005, modified 2012, deleted 2016]

1.14.13.17

Transferred entry:

cholesterol 7α-monooxygenase. Now EC 1.14.14.23, cholesterol 7α-monooxygenase

[EC 1.14.13.17 created 1976, deleted 2016]

1.14.13.98

Transferred entry:

cholesterol 24-hydroxylase. Now EC 1.14.14.25, cholesterol 24-hydroxylase

[EC 1.14.13.98 created 2005, deleted 2016]

1.14.13.99

Transferred entry:

24-hydroxycholesterol 7α-hydroxylase. Now EC 1.14.14.26, 24-hydroxycholesterol 7α-hydroxylase

[EC 1.14.13.99 created 2005, deleted 2016]

1.14.13.126

Transferred entry:

vitamin D₃ 24-hydroxylase. Now EC 1.14.15.16, vitamin D₃ 24-hydroxylase

[EC 1.14.13.126 created 2011, deleted 2016]

1.14.13.159

Transferred entry:

vitamin D 25-hydroxylase. Now EC 1.14.14.24, vitamin D 25-hydroxylase

[EC 1.14.13.159 created 2012, deleted 2016]

1.14.13.210

Accepted name:

4-methyl-5-nitrocatechol 5-monooxygenase

Reaction:

4-methyl-5-nitrocatechol + NAD(P)H + H⁺ + O₂ = 2-hydroxy-5-methylquinone + nitrite + NAD(P)⁺ + H₂O

Other name(s):

dntB (gene name); 4-methyl-5-nitrocatechol oxygenase; MNC monooxygenase

Systematic name:

4-methyl-5-nitrocatechol,NAD(P)H:oxygen 5-oxidoreductase (5-hydroxylating, nitrite-forming)

Comments:

Contains FAD. The enzyme, isolated from the bacterium Burkholderia sp. DNT, can use both NADH and NADPH, but prefers NADPH. It has a narrow substrate range, but can also act on 4-nitrocatechol.

Links to other databases:

References:

1.	Haigler, B.E., Suen, W.C. and Spain, J.C. Purification and sequence analysis of 4-methyl-5-nitrocatechol oxygenase from Burkholderia sp. strain DNT. J. Bacteriol. 178 (1996) 6019–6024. [DOI] [PMID: 8830701]
2.	Leungsakul, T., Johnson, G.R. and Wood, T.K. Protein engineering of the 4-methyl-5-nitrocatechol monooxygenase from Burkholderia sp. strain DNT for enhanced degradation of nitroaromatics. Appl. Environ. Microbiol. 72 (2006) 3933–3939. [DOI] [PMID: 16751499]

[EC 1.14.13.210 created 2016]

1.14.13.211

Accepted name:

rifampicin monooxygenase

Reaction:

rifampicin + NAD(P)H + O₂ = 2-hydroxy-2,27-secorifampicin + NAD(P)⁺ + H₂O

For diagram of rifampicin, click here

Glossary:

rifampicin = (2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-5,6,9,17,19-pentahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-{[(E)-(4-methylpiperazin-1-yl)imino]methyl}-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca-1,11,13-trienoimino)nathpho[2,1-b]furan-21-yl acetate

Other name(s):

RIF-O; ROX; RIFMO; rifampicin:NAD(P)H:oxygen oxidoreductase (2′-N-hydroxyrifampicin-forming) (incorrect)

Systematic name:

rifampicin:NAD(P)H:oxygen oxidoreductase (2-hydroxy-2,27-secorifampicin-forming; ring-cleaving)

Comments:

The enzyme has been found in a variety of environmental bacteria, notably Rhodococcus, Nocardia, and Streptomyces. It hydroxylates C-2 of rifampicin leading to its macro-ring cleaving.

Links to other databases:

References:

1.	Andersen, S.J., Quan, S., Gowan, B. and Dabbs, E.R. Monooxygenase-like sequence of a Rhodococcus equi gene conferring increased resistance to rifampin by inactivating this antibiotic. Antimicrob. Agents Chemother. 41 (1997) 218–221. [PMID: 8980786]
2.	Hoshino, Y., Fujii, S., Shinonaga, H., Arai, K., Saito, F., Fukai, T., Satoh, H., Miyazaki, Y. and Ishikawa, J. Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance. J. Antibiot. (Tokyo) 63 (2010) 23–28. [DOI] [PMID: 19942945]
3.	Koteva, K., Cox, G., Kelso, J.K., Surette, M.D., Zubyk, H.L., Ejim, L., Stogios, P., Savchenko, A., Sørensen, D. and Wright, G.D. Rox, a rifamycin resistance enzyme with an unprecedented mechanism of action. Cell Chem Biol 25 (2018) 403–412.e5. [DOI] [PMID: 29398560]
4.	Liu, L.K., Dai, Y., Abdelwahab, H., Sobrado, P. and Tanner, J.J. Structural evidence for rifampicin monooxygenase inactivating rifampicin by cleaving Its ansa-bridge. Biochemistry 57 (2018) 2065–2068. [DOI] [PMID: 29578336]

[EC 1.14.13.211 created 2016, modified 2022]

1.14.13.212

Accepted name:

1,3,7-trimethyluric acid 5-monooxygenase

Reaction:

1,3,7-trimethylurate + NADH + H⁺ + O₂ = 1,3,7-trimethyl-5-hydroxyisourate + NAD⁺ + H₂O

Glossary:

isourate = 1,3,5,7-tetrahydropurine-2,6,8-trione

Other name(s):

tmuM (gene name)

Systematic name:

1,3,7-trimethylurate,NADH:oxygen oxidoreductase (1,3,7-trimethyl-5-hydroxyisourate-forming)

Comments:

The enzyme, characterized from the bacterium Pseudomonas sp. CBB1, is part of the bacterial C-8 oxidation-based caffeine degradation pathway. The product decomposes spontaneously to a racemic mixture of 3,6,8-trimethylallantoin. The enzyme shows no acitivity with urate. cf. EC 1.14.13.113, FAD-dependent urate hydroxylase.

Links to other databases:

References:

1.	Mohanty, S.K., Yu, C.L., Das, S., Louie, T.M., Gakhar, L. and Subramanian, M. Delineation of the caffeine C-8 oxidation pathway in Pseudomonas sp. strain CBB1 via characterization of a new trimethyluric acid monooxygenase and genes involved in trimethyluric acid metabolism. J. Bacteriol. 194 (2012) 3872–3882. [DOI] [PMID: 22609920]
2.	Summers, R.M., Mohanty, S.K., Gopishetty, S. and Subramanian, M. Genetic characterization of caffeine degradation by bacteria and its potential applications. Microb. Biotechnol. 8 (2015) 369–378. [DOI] [PMID: 25678373]

[EC 1.14.13.212 created 2016]

1.14.13.213

Transferred entry:

bursehernin 5-monooxygenase. Now EC 1.14.14.131, bursehernin 5-monooxygenase

[EC 1.14.13.213 created 2016, deleted 2018]

1.14.13.214

Transferred entry:

(–)-4′-demethyl-deoxypodophyllotoxin 4-hydroxylase. Now EC 1.14.14.132, (–)-4′-demethyl-deoxypodophyllotoxin 4-hydroxylase

[EC 1.14.13.214 created 2016, deleted 2018]

1.14.13.215

Accepted name:

protoasukamycin 4-monooxygenase

Reaction:

protoasukamycin + NADH + H⁺ + O₂ = 4-hydroxyprotoasukamycin + NAD⁺ + H₂O

Glossary:

asuE1 (gene name)

Systematic name:

protoasukamycin,NADH:oxygen oxidoreductase (4-hydroxylating)

Comments:

The enzyme, characterized from the bacterium Streptomyces nodosus subsp. asukaensis, is involved in the biosynthesis of the antibiotic asukamycin. Requires a flavin cofactor, with no preference among FMN, FAD or riboflavin. When flavin concentration is low, activity is enhanced by the presence of the NADH-dependent flavin-reductase AsuE2.

Links to other databases:

References:

1.	Rui, Z., Sandy, M., Jung, B. and Zhang, W. Tandem enzymatic oxygenations in biosynthesis of epoxyquinone pharmacophore of manumycin-type metabolites. Chem. Biol. 20 (2013) 879–887. [DOI] [PMID: 23890006]

[EC 1.14.13.215 created 2016]

1.14.13.216

Accepted name:

asperlicin C monooxygenase

Reaction:

asperlicin C + NAD(P)H + H⁺ + O₂ = asperlicin E + NAD(P)⁺ + H₂O

Other name(s):

AspB

Systematic name:

asperlicin C,NAD(P)H:oxygen oxidoreductase

Comments:

The enzyme, characterized from the fungus Aspergillus alliaceus, contains an FAD cofactor. The enzyme inserts a hydroxyl group, leading to formation of a N-C bond that creates an additional cycle between the bicyclic indole and the tetracyclic core moieties, resulting in the heptacyclic asperlicin E.

Links to other databases:

References:

1.	Haynes, S.W., Gao, X., Tang, Y. and Walsh, C.T. Assembly of asperlicin peptidyl alkaloids from anthranilate and tryptophan: a two-enzyme pathway generates heptacyclic scaffold complexity in asperlicin E. J. Am. Chem. Soc. 134 (2012) 17444–17447. [DOI] [PMID: 23030663]

[EC 1.14.13.216 created 2016]

1.14.13.217

Accepted name:

protodeoxyviolaceinate monooxygenase

Reaction:

protodeoxyviolaceinate + NAD(P)H + O₂ = protoviolaceinate + NAD(P)⁺ + H₂O

For diagram of violacein biosynthesis, click here

Glossary:

protodeoxyviolaceinate = 3,5-di(1H-indol-3-yl)-1H-pyrrole-2-carboxylate
protoviolaceinate = 5-(5-hydroxy-1H-indol-3-yl)-3-(1H-indol-3-yl)-1H-pyrrole-2-carboxylate

Other name(s):

vioD (gene name); protoviolaceinate synthase

Systematic name:

protodeoxyviolaceinate,NAD(P)H:O₂ oxidoreductase

Comments:

The enzyme, characterized from the bacterium Chromobacterium violaceum, participates in the biosynthesis of the violet pigment violacein. The product, protoviolaceinate, can be acted upon by EC 1.14.13.224, violacein synthase, leading to violacein production. However, it is very labile, and in the presence of oxygen can undergo non-enzymic autooxidation to the shunt product proviolacein.

Links to other databases:

References:

1.	Balibar, C.J. and Walsh, C.T. In vitro biosynthesis of violacein from L-tryptophan by the enzymes VioA-E from Chromobacterium violaceum. Biochemistry 45 (2006) 15444–15457. [DOI] [PMID: 17176066]
2.	Shinoda, K., Hasegawa, T., Sato, H., Shinozaki, M., Kuramoto, H., Takamiya, Y., Sato, T., Nikaidou, N., Watanabe, T. and Hoshino, T. Biosynthesis of violacein: a genuine intermediate, protoviolaceinic acid, produced by VioABDE, and insight into VioC function. Chem. Commun. (Camb.) (2007) 4140–4142. [DOI] [PMID: 17925955]

[EC 1.14.13.217 created 2016, modified 2016]

1.14.14.20

Accepted name:

phenol 2-monooxygenase (FADH₂)

Reaction:

phenol + FADH₂ + O₂ = catechol + FAD + H₂O

Other name(s):

pheA1 (gene name)

Systematic name:

phenol,FADH₂:oxygen oxidoreductase (2-hydroxylating)

Comments:

The enzyme catalyses the ortho-hydroxylation of simple phenols into the corresponding catechols. It accepts 4-methylphenol, 4-chlorophenol, and 4-fluorophenol [1] as well as 4-nitrophenol, 3-nitrophenol, and resorcinol [3]. The enzyme is part of a two-component system that also includes an NADH-dependent flavin reductase. It is strictly dependent on FADH₂ and does not accept FMNH₂ [1,3]. cf. EC 1.14.13.7, phenol 2-monooxygenase (NADPH).

Links to other databases:

References:

1.	Kirchner, U., Westphal, A.H., Muller, R. and van Berkel, W.J. Phenol hydroxylase from Bacillus thermoglucosidasius A7, a two-protein component monooxygenase with a dual role for FAD. J. Biol. Chem. 278 (2003) 47545–47553. [DOI] [PMID: 12968028]
2.	van den Heuvel, R.H., Westphal, A.H., Heck, A.J., Walsh, M.A., Rovida, S., van Berkel, W.J. and Mattevi, A. Structural studies on flavin reductase PheA2 reveal binding of NAD in an unusual folded conformation and support novel mechanism of action. J. Biol. Chem. 279 (2004) 12860–12867. [DOI] [PMID: 14703520]
3.	Saa, L., Jaureguibeitia, A., Largo, E., Llama, M.J. and Serra, J.L. Cloning, purification and characterization of two components of phenol hydroxylase from Rhodococcus erythropolis UPV-1. Appl. Microbiol. Biotechnol. 86 (2010) 201–211. [DOI] [PMID: 19787347]

[EC 1.14.14.20 created 2016]

1.14.14.21

Accepted name:

dibenzothiophene monooxygenase

Reaction:

dibenzothiophene + 2 FMNH₂ + 2 O₂ = dibenzothiophene-5,5-dioxide + 2 FMN + 2 H₂O (overall reaction)
(1a) dibenzothiophene + FMNH₂ + O₂ = dibenzothiophene-5-oxide + FMN + H₂O
(1b) dibenzothiophene-5-oxide + FMNH₂ + O₂ = dibenzothiophene-5,5-dioxide + FMN + H₂O

Glossary:

dibenzothiophene-5,5-dioxide = dibenzothiophene sulfone

Other name(s):

dszC (gene name)

Systematic name:

dibenzothiophene,FMNH₂:oxygen oxidoreductase

Comments:

This bacterial enzyme catalyses the first two steps in the desulfurization pathway of dibenzothiophenes, the oxidation of dibenzothiophene into dibenzothiophene sulfone via dibenzothiophene-5-oxide. The enzyme forms a two-component system with a dedicated NADH-dependent FMN reductase (EC 1.5.1.42) encoded by the dszD gene, which also interacts with EC 1.14.14.22, dibenzothiophene sulfone monooxygenase.

Links to other databases:

References:

1.	Gray, K.A., Pogrebinsky, O.S., Mrachko, G.T., Xi, L., Monticello, D.J. and Squires, C.H. Molecular mechanisms of biocatalytic desulfurization of fossil fuels. Nat. Biotechnol. 14 (1996) 1705–1709. [DOI] [PMID: 9634856]
2.	Liu, S., Zhang, C., Su, T., Wei, T., Zhu, D., Wang, K., Huang, Y., Dong, Y., Yin, K., Xu, S., Xu, P. and Gu, L. Crystal structure of DszC from Rhodococcus sp. XP at 1.79 Å. Proteins 82 (2014) 1708–1720. [DOI] [PMID: 24470304]
3.	Guan, L.J., Lee, W.C., Wang, S., Ohshiro, T., Izumi, Y., Ohtsuka, J. and Tanokura, M. Crystal structures of apo-DszC and FMN-bound DszC from Rhodococcus erythropolis D-1. FEBS J. 282 (2015) 3126–3135. [DOI] [PMID: 25627402]

[EC 1.14.14.21 created 2016]

1.14.14.22

Accepted name:

dibenzothiophene sulfone monooxygenase

Reaction:

dibenzothiophene-5,5-dioxide + FMNH₂ + NADH + O₂ = 2′-hydroxybiphenyl-2-sulfinate + H₂O + FMN + NAD⁺ + H⁺ (overall reaction)
(1a) FMNH₂ + O₂ = FMN-N⁵-peroxide
(1b) dibenzothiophene-5,5-dioxide + FMN-N⁵-peroxide = 2′-hydroxybiphenyl-2-sulfinate + FMN-N⁵-oxide
(1c) FMN-N⁵-oxide + NADH = FMN + H₂O + NAD⁺ + H⁺ (spontaneous)

Glossary:

dibenzothiophene-5,5-dioxide = dibenzothiophene sulfone

Other name(s):

dszA (gene name)

Systematic name:

dibenzothiophene-5,5-dioxide,FMNH₂:oxygen oxidoreductase

Comments:

This bacterial enzyme catalyses a step in the desulfurization pathway of dibenzothiophenes. The enzyme forms a two-component system with a dedicated NADH-dependent FMN reductase (EC 1.5.1.42) encoded by the dszD gene, which also interacts with EC 1.14.14.21, dibenzothiophene monooxygenase. The flavin-N⁵-oxide that is formed by the enzyme reacts spontaneously with NADH to give oxidized flavin, releasing a water molecule.

Links to other databases:

References:

1.	Gray, K.A., Pogrebinsky, O.S., Mrachko, G.T., Xi, L., Monticello, D.J. and Squires, C.H. Molecular mechanisms of biocatalytic desulfurization of fossil fuels. Nat. Biotechnol. 14 (1996) 1705–1709. [DOI] [PMID: 9634856]
2.	Ohshiro, T., Kojima, T., Torii, K., Kawasoe, H. and Izumi, Y. Purification and characterization of dibenzothiophene (DBT) sulfone monooxygenase, an enzyme involved in DBT desulfurization, from Rhodococcus erythropolis D-1. J. Biosci. Bioeng. 88 (1999) 610–616. [DOI] [PMID: 16232672]
3.	Konishi, J., Ishii, Y., Onaka, T., Ohta, Y., Suzuki, M. and Maruhashi, K. Purification and characterization of dibenzothiophene sulfone monooxygenase and FMN-dependent NADH oxidoreductase from the thermophilic bacterium Paenibacillus sp. strain A11-2. J. Biosci. Bioeng. 90 (2000) 607–613. [DOI] [PMID: 16232919]
4.	Ohshiro, T., Ishii, Y., Matsubara, T., Ueda, K., Izumi, Y., Kino, K. and Kirimura, K. Dibenzothiophene desulfurizing enzymes from moderately thermophilic bacterium Bacillus subtilis WU-S₂B: purification, characterization and overexpression. J. Biosci. Bioeng. 100 (2005) 266–273. [DOI] [PMID: 16243275]
5.	Adak, S. and Begley, T.P. Dibenzothiophene catabolism proceeds via a flavin-N⁵-oxide intermediate. J. Am. Chem. Soc. 138 (2016) 6424–6426. [PMID: 27120486]
6.	Adak, S. and Begley, T.P. Flavin-N⁵-oxide: A new, catalytic motif in flavoenzymology. Arch. Biochem. Biophys. 632 (2017) 4–10. [PMID: 28784589]
7.	Matthews, A., Saleem-Batcha, R., Sanders, J.N., Stull, F., Houk, K.N. and Teufel, R. Aminoperoxide adducts expand the catalytic repertoire of flavin monooxygenases. Nat. Chem. Biol. 16 (2020) 556–563. [DOI] [PMID: 32066967]

[EC 1.14.14.22 created 2016, modified 2019]

1.14.14.23

Accepted name:

cholesterol 7α-monooxygenase

Reaction:

cholesterol + [reduced NADPH—hemoprotein reductase] + O₂ = 7α-hydroxycholesterol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of cholesterol catabolism (rings A, B and C), click here

Other name(s):

cholesterol 7α-hydroxylase; CYP7A1 (gene name)

Systematic name:

cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (7α-hydroxylating)

Comments:

A P-450 heme-thiolate liver protein that catalyses the first step in the biosynthesis of bile acids. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 9037-53-0

References:

1.	Mitton, J.R., Scholan, N.A. and Boyd, G.S. The oxidation of cholesterol in rat liver sub-cellular particles. The cholesterol-7α-hydroxylase enzyme system. Eur. J. Biochem. 20 (1971) 569–579. [DOI] [PMID: 4397276]
2.	Boyd, G.S., Grimwade, A.M. and Lawson, M.E. Studies on rat-liver microsomal cholesterol 7α-hydroxylase. Eur. J. Biochem. 37 (1973) 334–340. [DOI] [PMID: 4147676]
3.	Ogishima, T., Deguchi, S. and Okuda, K. Purification and characterization of cholesterol 7α-hydroxylase from rat liver microsomes. J. Biol. Chem. 262 (1987) 7646–7650. [PMID: 3584134]
4.	Nguyen, L.B., Shefer, S., Salen, G., Ness, G., Tanaka, R.D., Packin, V., Thomas, P., Shore, V. and Batta, A. Purification of cholesterol 7 α-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies. J. Biol. Chem. 265 (1990) 4541–4546. [PMID: 2106520]
5.	Nguyen, L.B., Shefer, S., Salen, G., Chiang, J.Y. and Patel, M. Cholesterol 7α-hydroxylase activities from human and rat liver are modulated in vitro posttranslationally by phosphorylation/dephosphorylation. Hepatology 24 (1996) 1468–1474. [DOI] [PMID: 8938182]

[EC 1.14.14.23 created 1976 as EC 1.14.13.17, transferred 2016 to EC 1.14.14.23]

1.14.14.24

Accepted name:

vitamin D 25-hydroxylase

Reaction:

calciol + O₂ + [reduced NADPH—hemoprotein reductase] = calcidiol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of calciferol biosynthesis, click here

Glossary:

calciol = cholecalciferol = vitamin D₃ = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol
calcidiol = 25-hydroxyvitamin D₃ = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol

Other name(s):

vitamin D₂ 25-hydroxylase; vitamin D₃ 25-hydroxylase; CYP2R1

Systematic name:

calciol,NADPH—hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)

Comments:

A microsomal enzyme isolated from human and mouse liver that bioactivates vitamin D₃. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo [4]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases:

References:

1.	Cheng, J.B., Motola, D.L., Mangelsdorf, D.J. and Russell, D.W. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J. Biol. Chem. 278 (2003) 38084–38093. [DOI] [PMID: 12867411]
2.	Shinkyo, R., Sakaki, T., Kamakura, M., Ohta, M. and Inouye, K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem. Biophys. Res. Commun. 324 (2004) 451–457. [DOI] [PMID: 15465040]
3.	Strushkevich, N., Usanov, S.A., Plotnikov, A.N., Jones, G. and Park, H.W. Structural analysis of CYP2R1 in complex with vitamin D₃. J. Mol. Biol. 380 (2008) 95–106. [DOI] [PMID: 18511070]
4.	Zhu, J. and DeLuca, H.F. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch. Biochem. Biophys. 523 (2012) 30–36. [DOI] [PMID: 22310641]

[EC 1.14.14.24 created 2012 as EC 1.14.13.159, transferred 2016 to EC 1.14.14.24]

1.14.14.25

Accepted name:

cholesterol 24-hydroxylase

Reaction:

cholesterol + [reduced NADPH—hemoprotein reductase] + O₂ = (24S)-cholest-5-ene-3β,24-diol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of cholic acid biosynthesis (sidechain), click here

Glossary:

cholesterol = cholest-5-en-3β-ol
(24S)-24-hydroxycholesterol = (24S)-cholest-5-ene-3β,24-diol

Other name(s):

cholesterol 24-monooxygenase; CYP46; CYP46A1; cholesterol 24S-hydroxylase; cytochrome P450 46A1

Systematic name:

cholesterol,NADPH—hemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)

Comments:

A P-450 heme-thiolate protein. The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol [2]. This reaction is the first step in the enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood—brain barrier whereas cholesterol cannot [3]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase [3].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 50812-30-1, 213327-78-7

References:

1.	Lund, E.G., Guileyardo, J.M. and Russell, D.W. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc. Natl. Acad. Sci. USA 96 (1999) 7238–7243. [DOI] [PMID: 10377398]
2.	Bogdanovic, N., Bretillon, L., Lund, E.G., Diczfalusy, U., Lannfelt, L., Winblad, B., Russell, D.W. and Björkhem, I. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci. Lett. 314 (2001) 45–48. [DOI] [PMID: 11698143]
3.	Mast, N., Norcross, R., Andersson, U., Shou, M., Nakayama, K., Bjorkhem, I. and Pikuleva, I.A. Broad substrate specificity of human cytochrome P₄₅₀ 46A1 which initiates cholesterol degradation in the brain. Biochemistry 42 (2003) 14284–14292. [DOI] [PMID: 14640697]
4.	Lund, E.G., Xie, C., Kotti, T., Turley, S.D., Dietschy, J.M. and Russell, D.W. Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover. J. Biol. Chem. 278 (2003) 22980–22988. [DOI] [PMID: 12686551]
5.	Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]

[EC 1.14.14.25 created 2005 as EC 1.14.13.98, transferred 2016 to EC 1.14.14.25]

1.14.14.26

Accepted name:

24-hydroxycholesterol 7α-hydroxylase

Reaction:

(24S)-cholest-5-ene-3β,24-diol + [reduced NADPH—hemoprotein reductase] + O₂ = (24S)-cholest-5-ene-3β,7α,24-triol + [oxidized NADPH—hemoprotein reductase] + H₂O

For diagram of cholesterol catabolism (rings a, B and c), click here

Glossary:

(24S)-cholest-5-ene-3β,24-diol = (24S)-24-hydroxycholesterol

Other name(s):

24-hydroxycholesterol 7α-monooxygenase; CYP39A1; CYP39A1 oxysterol 7α-hydroxylase

Systematic name:

(24S)-cholest-5-ene-3β,24-diol,NADPH—hemoprotein reductase:oxygen oxidoreductase (7α-hydroxylating)

Comments:

A P-450 heme-thiolate protein that is found in liver microsomes and in ciliary non-pigmented epithelium [2]. The enzyme is specific for (24S)-cholest-5-ene-3β,24-diol, which is formed mostly in the brain by EC 1.14.14.25, cholesterol 24-hydroxylase. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH—hemoprotein reductase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 288309-90-0

References:

1.	Li-Hawkins, J., Lund, E.G., Bronson, A.D. and Russell, D.W. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J. Biol. Chem. 275 (2000) 16543–16549. [DOI] [PMID: 10748047]
2.	Ikeda, H., Ueda, M., Ikeda, M., Kobayashi, H. and Honda, Y. Oxysterol 7alpha-hydroxylase (CYP39A1) in the ciliary nonpigmented epithelium of bovine eye. Lab. Invest. 83 (2003) 349–355. [PMID: 12649335]
3.	Russell, D.W. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003) 137–174. [DOI] [PMID: 12543708]

[EC 1.14.14.26 created 2005 as EC 1.14.13.99, transferred 2016 to EC 1.14.14.26]

*EC

1.14.15.9

Accepted name:

spheroidene monooxygenase

Reaction:

(1) spheroidene + 4 reduced ferredoxin [iron-sulfur] cluster + 2 O₂ + 4 H⁺ = spheroiden-2-one + 4 oxidized ferredoxin [iron-sulfur] cluster + 3 H₂O (overall reaction)
(1a) spheroidene + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = 2-hydroxyspheroidene + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(1b) 2-hydroxyspheroidene + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = 2,2-dihydroxyspheroidene + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(1c) 2,2-dihydroxyspheroidene = spheroiden-2-one + H₂O (spontaneous)
(2) spirilloxanthin + 4 reduced ferredoxin [iron-sulfur] cluster + 2 O₂ + 4 H⁺ = 2-oxospirilloxanthin + 4 oxidized ferredoxin [iron-sulfur] cluster + 3 H₂O (overall reaction)
(2a) spirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = 2-hydroxyspirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(2b) 2-hydroxyspirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = 2,2-dihydroxyspirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(2c) 2,2-dihydroxyspirilloxanthin = 2-oxospirilloxanthin + H₂O (spontaneous)
(3) 2-oxospirilloxanthin + 4 reduced ferredoxin [iron-sulfur] cluster + 2 O₂ + 4 H⁺ = 2,2′-dioxospirilloxanthin + 4 oxidized ferredoxin [iron-sulfur] cluster + 3 H₂O (overall reaction)
(3a) 2-oxospirilloxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = 2′-hydroxy-2-oxospirilloxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(3b) 2′-hydroxy-2-oxospirilloxanthin + reduced ferredoxin [iron-sulfur] cluster + O₂ + 2 H⁺ = 2′,2′-dihydroxy-2-oxospirilloxanthin + oxidized ferredoxin [iron-sulfur] cluster + H₂O
(3c) 2′,2′-dihydroxy-2-oxospirilloxanthin = 2,2′-dioxospirilloxanthin + H₂O (spontaneous)

For diagram of 2,2′-dioxospirilloxanthin biosynthesis, click here and for diagram of 4.2.1.131, click here

Glossary:

spheroidene = 3,4-didehydro-1-methoxy-1,2,7′,8′-tetrahydro-ψ,ψ-carotene

Other name(s):

CrtA; acyclic carotenoid 2-ketolase; spirilloxanthin monooxygenase; 2-oxo-spirilloxanthin monooxygenase

Systematic name:

spheroidene,reduced-ferredoxin:oxygen oxidoreductase (spheroiden-2-one-forming)

Comments:

The enzyme is involved in spheroidenone biosynthesis and in 2,2′-dioxospirilloxanthin biosynthesis. The enzyme from Rhodobacter sphaeroides contains heme at its active site [1].

Links to other databases:

References:

1.	Lee, P.C., Holtzapple, E. and Schmidt-Dannert, C. Novel activity of Rhodobacter sphaeroides spheroidene monooxygenase CrtA expressed in Escherichia coli. Appl. Environ. Microbiol. 76 (2010) 7328–7331. [DOI] [PMID: 20851979]
2.	Gerjets, T., Steiger, S. and Sandmann, G. Catalytic properties of the expressed acyclic carotenoid 2-ketolases from Rhodobacter capsulatus and Rubrivivax gelatinosus. Biochim. Biophys. Acta 1791 (2009) 125–131. [DOI] [PMID: 19136077]

[EC 1.14.15.9 created 2012, modified 2016]

1.14.15.15

Accepted name:

cholestanetriol 26-monooxygenase

Reaction:

5β-cholestane-3α,7α,12α-triol + 6 reduced adrenodoxin + 6 H⁺ + 3 O₂ = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 6 oxidized adrenodoxin + 4 H₂O (overall reaction)
(1a) 5β-cholestane-3α,7α,12α-triol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 oxidized adrenodoxin + H₂O
(1b) (25R)-5β-cholestane-3α,7α,12α,26-tetraol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 oxidized adrenodoxin + 2 H₂O
(1c) (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 reduced adrenodoxin + 2 H⁺ + O₂ = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 2 oxidized adrenodoxin + H₂O

For diagram of cholic acid biosynthesis (sidechain), click here

Other name(s):

5β-cholestane-3α,7α,12α-triol 26-hydroxylase; 5β-cholestane-3α,7α,12α-triol hydroxylase; cholestanetriol 26-hydroxylase; sterol 27-hydroxylase; sterol 26-hydroxylase; cholesterol 27-hydroxylase; CYP27A; CYP27A1; cytochrome P450 27A1′

Systematic name:

5β-cholestane-3α,7α,12α-triol,adrenodoxin:oxygen oxidoreductase (26-hydroxylating)

Comments:

This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3β,7α-diol, 7α-hydroxycholest-4-en-3-one, and 5β-cholestane-3α,7α-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP⁺ reductase.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 52227-77-7

References:

1.	Masui, T., Herman, R. and Staple, E. The oxidation of 5β-cholestane-3α,7α,12α,26-tetraol to 5β-cholestane-3α,7α,12α-triol-26-oic acid via 5β-cholestane-3α,7α,12α-triol-26-al by rat liver. Biochim. Biophys. Acta 117 (1966) 266–268. [DOI] [PMID: 5914340]
2.	Okuda, K. and Hoshita, N. Oxidation of 5β-cholestane-3α,7α,12α-triol by rat-liver mitochondria. Biochim. Biophys. Acta 164 (1968) 381–388. [DOI] [PMID: 4388637]
3.	Wikvall, K. Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C₂₇-steroids. J. Biol. Chem. 259 (1984) 3800–3804. [PMID: 6423637]
4.	Andersson, S., Davis, D.L., Dahlbäck, H., Jörnvall, H. and Russell, D.W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J. Biol. Chem. 264 (1989) 8222–8229. [PMID: 2722778]
5.	Dahlback, H. and Holmberg, I. Oxidation of 5β-cholestane-3α,7α,12α-triol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid by cytochrome P-450₂₆ from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 167 (1990) 391–395. [DOI] [PMID: 2322231]
6.	Holmberg-Betsholtz, I., Lund, E., Björkhem, I. and Wikvall, K. Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5β-cholestane-3α,7α,12α,27-tetrol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid. J. Biol. Chem. 268 (1993) 11079–11085. [PMID: 8496170]
7.	Pikuleva, I.A., Babiker, A., Waterman, M.R. and Bjorkhem, I. Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways. J. Biol. Chem. 273 (1998) 18153–18160. [DOI] [PMID: 9660774]
8.	Furster, C., Bergman, T. and Wikvall, K. Biochemical characterization of a truncated form of CYP27A purified from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 263 (1999) 663–666. [DOI] [PMID: 10512735]
9.	Pikuleva, I.A., Puchkaev, A. and Björkhem, I. Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P₄₅₀ 27A1. Biochemistry 40 (2001) 7621–7629. [DOI] [PMID: 11412116]

[EC 1.14.15.15 created 1976 as EC 1.14.13.15, modified 2005, modified 2012, transferred 2016 to EC 1.14.15.15]

1.14.15.16

Accepted name:

vitamin D₃ 24-hydroxylase

Reaction:

(1) calcitriol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = calcitetrol + 2 oxidized adrenodoxin + H₂O
(2) calcidiol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = secalciferol + 2 oxidized adrenodoxin + H₂O

For diagram of calciferol biosynthesis, click here

Glossary:

calcidiol = 25-hydroxyvitamin D₃ = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D₃ = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol
calcitetrol = 1α,24R,25-trihydroxyvitamin D₃ = (1S,3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-1,3,24,25-tetrol
secalciferol = (24R)-24,25-dihydroxycalciol = 24R,25-dihydroxyvitamin D₃ = (3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-3,24,25-triol

Other name(s):

CYP24A1

Systematic name:

calcitriol,adrenodoxin:oxygen oxidoreductase (24-hydroxylating)

Comments:

This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. The enzyme can perform up to 6 rounds of hydroxylation of the substrate calcitriol leading to calcitroic acid. The human enzyme also shows 23-hydroxylating activity leading to 1,25 dihydroxyvitamin D₃-26,23-lactone as end product while the mouse and rat enzymes do not. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP⁺ reductase.

Links to other databases:

References:

1.	Masuda, S., Strugnell, S.A., Knutson, J.C., St-Arnaud, R. and Jones, G. Evidence for the activation of 1α-hydroxyvitamin D₂ by 25-hydroxyvitamin D-24-hydroxylase: delineation of pathways involving 1α,24-dihydroxyvitamin D₂ and 1α,25-dihydroxyvitamin D₂. Biochim. Biophys. Acta 1761 (2006) 221–234. [DOI] [PMID: 16516540]
2.	Hamamoto, H., Kusudo, T., Urushino, N., Masuno, H., Yamamoto, K., Yamada, S., Kamakura, M., Ohta, M., Inouye, K. and Sakaki, T. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol. Pharmacol. 70 (2006) 120–128. [DOI] [PMID: 16617161]
3.	Sakaki, T., Kagawa, N., Yamamoto, K. and Inouye, K. Metabolism of vitamin D₃ by cytochromes P₄₅₀. Front. Biosci. 10 (2005) 119–134. [PMID: 15574355]
4.	Prosser, D.E., Kaufmann, M., O'Leary, B., Byford, V. and Jones, G. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1α,25-(OH)₂D₃-26,23-lactone. Proc. Natl. Acad. Sci. USA 104 (2007) 12673–12678. [DOI] [PMID: 17646648]
5.	Kusudo, T., Sakaki, T., Abe, D., Fujishima, T., Kittaka, A., Takayama, H., Hatakeyama, S., Ohta, M. and Inouye, K. Metabolism of A-ring diastereomers of 1α,25-dihydroxyvitamin D₃ by CYP24A1. Biochem. Biophys. Res. Commun. 321 (2004) 774–782. [DOI] [PMID: 15358094]
6.	Sawada, N., Kusudo, T., Sakaki, T., Hatakeyama, S., Hanada, M., Abe, D., Kamao, M., Okano, T., Ohta, M. and Inouye, K. Novel metabolism of 1α,25-dihydroxyvitamin D₃ with C₂₄-C₂₅ bond cleavage catalyzed by human CYP24A1. Biochemistry 43 (2004) 4530–4537. [DOI] [PMID: 15078099]
7.	Prosser, D.E. and Jones, G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 29 (2004) 664–673. [DOI] [PMID: 15544953]

[EC 1.14.15.16 created 2011 as EC 1.14.13.126, transferred 2016 to EC 1.14.15.16]

1.14.15.17

Accepted name:

pheophorbide a oxygenase

Reaction:

pheophorbide a + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = red chlorophyll catabolite + 2 oxidized ferredoxin [iron-sulfur] cluster (overall reaction)
(1a) pheophorbide a + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺ + O₂ = epoxypheophorbide a + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O
(1b) epoxypheophorbide a + H₂O = red chlorophyll catabolite (spontaneous)

For diagram of chlorophyll catabolism, click here

Glossary:

red chlorophyll catabolite = RCC = (7S,8S,10¹R)-8-(2-carboxyethyl)-8,23-dihydro-17-ethyl-19-formyl-10¹-(methoxycarbonyl)-3,7,13,18-tetramethyl-2-vinyl-7H-10,12-ethanobiladiene-ab-1,10²(21H)-dione

Other name(s):

pheide a monooxygenase; pheide a oxygenase; PaO; PAO

Systematic name:

pheophorbide-a,ferredoxin:oxygen oxidoreductase (biladiene-forming)

Comments:

This enzyme catalyses a key reaction in chlorophyll degradation, which occurs during leaf senescence and fruit ripening in higher plants. The enzyme from Arabidopsis contains a Rieske-type iron-sulfur cluster [2] and requires reduced ferredoxin, which is generated either by NADPH through the pentose-phosphate pathway or by the action of photosystem I [4]. While still attached to this enzyme, the product is rapidly converted into primary fluorescent chlorophyll catabolite by the action of EC 1.3.7.12, red chlorophyll catabolite reductase [2,6]. Pheophorbide b acts as an inhibitor. In ¹⁸O₂ labelling experiments, only the aldehyde oxygen is labelled, suggesting that the other oxygen atom may originate from H₂O [1].

Links to other databases:

References:

1.	Hörtensteiner, S., Wüthrich, K.L., Matile, P., Ongania, K.H. and Kräutler, B. The key step in chlorophyll breakdown in higher plants. Cleavage of pheophorbide a macrocycle by a monooxygenase. J. Biol. Chem. 273 (1998) 15335–15339. [DOI] [PMID: 9624113]
2.	Pružinská, A., Tanner, G., Anders, I., Roca, M. and Hörtensteiner, S. Chlorophyll breakdown: pheophorbide a oxygenase is a Rieske-type iron-sulfur protein, encoded by the accelerated cell death 1 gene. Proc. Natl. Acad. Sci. USA 100 (2003) 15259–15264. [DOI] [PMID: 14657372]
3.	Chung, D.W., Pružinská, A., Hörtensteiner, S. and Ort, D.R. The role of pheophorbide a oxygenase expression and activity in the canola green seed problem. Plant Physiol. 142 (2006) 88–97. [DOI] [PMID: 16844830]
4.	Rodoni, S., Mühlecker, W., Anderl, M., Kräutler, B., Moser, D., Thomas, H., Matile, P. and Hörtensteiner, S. Chlorophyll breakdown in senescent chloroplasts. Cleavage of pheophorbide a in two enzymic steps. Plant Physiol. 115 (1997) 669–676. [PMID: 12223835]
5.	Hörtensteiner, S. Chlorophyll degradation during senescence. Annu. Rev. Plant Biol. 57 (2006) 55–77. [DOI] [PMID: 16669755]
6.	Pružinská, A., Anders, I., Aubry, S., Schenk, N., Tapernoux-Lüthi, E., Müller, T., Kräutler, B. and Hörtensteiner, S. In vivo participation of red chlorophyll catabolite reductase in chlorophyll breakdown. Plant Cell 19 (2007) 369–387. [DOI] [PMID: 17237353]

[EC 1.14.15.17 created 2007 as EC 1.14.12.20, transferred 2016 to EC 1.14.15.17]

1.14.21.11

Transferred entry:

(–)-pluviatolide synthase. Now EC 1.14.19.72, (–)-pluviatolide synthase

[EC 1.14.21.11 created 2016, deleted 2018]

1.14.99.9

Transferred entry:

steroid 17α-monooxygenase, now classified as EC 1.14.14.19, steroid 17α-monooxygenase

[EC 1.14.99.9 created 1961 as EC 1.99.1.9, transferred 1965 to EC 1.14.1.7, transferred 1972 to EC 1.14.99.9, modified 2013, deleted 2015]

1.17.1.2

Transferred entry:

4-hydroxy-3-methylbut-2-enyl diphosphate reductase, now classified as EC 1.17.7.4, 4-hydroxy-3-methylbut-2-enyl diphosphate reductase.

[EC 1.17.1.2 created 2003, modified 2009, deleted 2016]

1.17.7.4

Accepted name:

4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase

Reaction:

(1) 3-methylbut-3-en-1-yl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺
(2) prenyl diphosphate + 2 oxidized ferredoxin [iron-sulfur] cluster + H₂O = (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H⁺

For diagram of Non-Mevalonate terpenoid biosynthesis, click here

Glossary:

isopentenyl = 3-methylbut-3-en-1-yl
prenyl = 3-methylbut-2-en-1-yl

Other name(s):

isopentenyl-diphosphate:NADP⁺ oxidoreductase; LytB; (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase; HMBPP reductase; IspH; LytB/IspH; isopentenyl-diphosphate:ferredoxin oxidoreductase

Systematic name:

3-methylbut-3-en-1-yl-diphosphate:ferredoxin oxidoreductase

Comments:

An iron-sulfur protein that contains an unusual [4Fe-4S] cluster [5,6]. This enzyme forms a system with a ferredoxin or a flavodoxin and an NAD(P)H-dependent reductase. This is the last enzyme in the non-mevalonate pathway for isoprenoid biosynthesis. This pathway, also known as the 1-deoxy-D-xylulose 5-phosphate (DOXP) or as the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, is found in most bacteria and in plant chloroplasts. The enzyme acts in the reverse direction, producing a 5:1 mixture of 3-methylbut-3-en-1-yl diphosphate and prenyl diphosphate.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 512789-14-9

References:

1.	Rohdich, F., Hecht, S., Gärtner, K., Adam, P., Krieger, C., Amslinger, S., Arigoni, D., Bacher, A. and Eisenreich, W. Studies on the nonmevalonate terpene biosynthetic pathway: Metabolic role of IspH (LytB) protein. Proc. Natl. Acad. Sci. USA 99 (2002) 1158–1163. [DOI] [PMID: 11818558]
2.	Hintz, M., Reichenberg, A., Altincicek, B., Bahr, U., Gschwind, R.M., Kollas, A.-K., Beck, E., Wiesner, J., Eberl, M. and Jomaa, H. Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human T cells in Escherichia coli. FEBS Lett. 509 (2001) 317–322. [DOI] [PMID: 11741609]
3.	Charon, L., Pale-Grosdemange, C. and Rohmer, M. On the reduction steps in the mevalonate independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in the bacterium Zymomonas mobilis. Tetrahedron Lett. 40 (1999) 7231–7234. [DOI]
4.	Röhrich, R.C., Englert, N., Troschke, K., Reichenberg, A., Hintz, M., Seeber, F., Balconi, E., Aliverti, A., Zanetti, G., Köhler, U., Pfeiffer, M., Beck, E., Jomaa, H. and Wiesner, J. Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum. FEBS Lett. 579 (2005) 6433–6438. [DOI] [PMID: 16289098]
5.	Wolff, M., Seemann, M., Bui, T.S.B., Frapart, Y., Tritsch, D., Garcia Estrabot, A., Rodríguez-Concepción, M., Boronat, A., Marquet, A. and Rohmer, M. Isoprenoid biosynthesis via the methylerythritol phosphate pathway: the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB/IspH) from Escherichia coli is a [4Fe-4S] protein. FEBS Lett. 541 (2003) 115–120. [DOI] [PMID: 12706830]
6.	Faus, I., Reinhard, A., Rackwitz, S., Wolny, J.A., Schlage, K., Wille, H.C., Chumakov, A., Krasutsky, S., Chaignon, P., Poulter, C.D., Seemann, M. and Schunemann, V. Isoprenoid biosynthesis in pathogenic bacteria: nuclear resonance vibrational spectroscopy provides insight into the unusual [4Fe-4S] cluster of the E. coli LytB/IspH protein. Angew. Chem. Int. Ed. Engl. 54 (2015) 12584–12587. [DOI] [PMID: 26118554]

[EC 1.17.7.4 created 2003 as EC 1.17.1.2, modified 2009, transferred 2016 to EC 1.17.7.4]

*EC

1.18.1.6

Accepted name:

adrenodoxin-NADP⁺ reductase

Reaction:

2 reduced adrenodoxin + NADP⁺ + H⁺ = 2 oxidized adrenodoxin + NADPH

Other name(s):

adrenodoxin reductase; nicotinamide adenine dinucleotide phosphate-adrenodoxin reductase; AdR; NADPH:adrenal ferredoxin oxidoreductase; NADPH-adrenodoxin reductase

Systematic name:

reduced adrenodoxin:NADP⁺ oxidoreductase

Comments:

A flavoprotein (FAD). The enzyme, which transfers electrons from NADPH to adrenodoxin molecules, is the first component of the mitochondrial cytochrome P-450 electron transfer systems, and is involved in the biosynthesis of all steroid hormones.

Links to other databases:

References:

1.	Omura, T., Sanders, E., Estabrook, R.W., Cooper, D.Y. and Rosenthal, O. Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase. Arch. Biochem. Biophys. 117 (1966) 660–673.
2.	Chu, J.W. and Kimura, T. Studies on adrenal steroid hydroxylases. Molecular and catalytic properties of adrenodoxin reductase (a flavoprotein). J. Biol. Chem. 248 (1973) 2089–2094. [PMID: 4144106]
3.	Sugiyama, T. and Yamano, T. Purification and crystallization of NADPH-adrenodoxin reductase from bovine adrenocortical mitochondria. FEBS Lett. 52 (1975) 145–148. [DOI] [PMID: 235468]
4.	Hanukoglu, I. and Jefcoate, C.R. Mitochondrial cytochrome P-450_scc. Mechanism of electron transport by adrenodoxin. J. Biol. Chem. 255 (1980) 3057–3061. [PMID: 6766943]
5.	Hanukoglu, I. and Hanukoglu, Z. Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation. Eur. J. Biochem. 157 (1986) 27–31. [DOI] [PMID: 3011431]
6.	Hanukoglu, I. and Gutfinger, T. cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases. Eur. J. Biochem. 180 (1989) 479–484. [DOI] [PMID: 2924777]
7.	Ziegler, G.A., Vonrhein, C., Hanukoglu, I. and Schulz, G.E. The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis. J. Mol. Biol. 289 (1999) 981–990. [DOI] [PMID: 10369776]

[EC 1.18.1.6 created 1965 as EC 1.6.99.4, transferred 1972 as EC 1.6.7.1, transferred 1978 to EC 1.18.1.2, part transferred 2012 to EC 1.18.1.6, modified 2016]

1.21.3.9

Transferred entry:

dichlorochromopyrrolate synthase, now classified as EC 1.21.98.2, dichlorochromopyrrolate synthase

[EC 1.21.3.9 created 2010 as EC 4.3.1.26, transferred 2013 to EC 1.21.3.9, deleted 2016]

1.21.98.2

Accepted name:

dichlorochromopyrrolate synthase

Reaction:

2 3-(7-chloroindol-3-yl)-2-iminopropanoate + H₂O₂ = dichlorochromopyrrolate + NH₃ + 2 H₂O

For diagram of rebeccamycin biosynthesis, click here

Glossary:

dichlorochromopyrrolate = 3,4-bis(7-chloro-1H-indol-3-yl)-1H-pyrrole-2,5-dicarboxylate

Other name(s):

RebD; chromopyrrolic acid synthase; chromopyrrolate synthase

Systematic name:

3-(7-chloroindol-3-yl)-2-iminopropanoate ammonia-lyase (dichlorochromopyrrolate-forming)

Comments:

This enzyme catalyses a step in the biosynthesis of rebeccamycin, an indolocarbazole alkaloid produced by the bacterium Lechevalieria aerocolonigenes. The enzyme is a dimeric heme-protein oxidase that catalyses the oxidative dimerization of two L-tryptophan-derived molecules to form dichlorochromopyrrolic acid, the precursor for the fused six-ring indolocarbazole scaffold of rebeccamycin [1]. Contains one molecule of heme b per monomer, as well as non-heme iron that is not part of an iron-sulfur center [2]. In vivo the enzyme uses hydrogen peroxide, formed by the enzyme upstream in the biosynthetic pathway (EC 1.4.3.23, 7-chloro-L-tryptophan oxidase) as the electron acceptor. However, the enzyme is also able to catalyse the reaction using molecular oxygen [3].

Links to other databases:

References:

1.	Nishizawa, T., Gruschow, S., Jayamaha, D.H., Nishizawa-Harada, C. and Sherman, D.H. Enzymatic assembly of the bis-indole core of rebeccamycin. J. Am. Chem. Soc. 128 (2006) 724–725. [DOI] [PMID: 16417354]
2.	Howard-Jones, A.R. and Walsh, C.T. Enzymatic generation of the chromopyrrolic acid scaffold of rebeccamycin by the tandem action of RebO and RebD. Biochemistry 44 (2005) 15652–15663. [DOI] [PMID: 16313168]
3.	Spolitak, T. and Ballou, D.P. Evidence for catalytic intermediates involved in generating the chromopyrrolic acid scaffold of rebeccamycin by RebO and RebD. Arch. Biochem. Biophys. 573 (2015) 111–119. [DOI] [PMID: 25837855]

[EC 1.21.98.2 created 2010 as EC 4.3.1.26, transferred 2013 to EC 1.21.3.9, transferred 2016 to EC 1.21.98.2]

2.1.1.323

Accepted name:

(–)-pluviatolide 4-O-methyltransferase

Reaction:

S-adenosyl-L-methionine + (–)-pluviatolide = S-adenosyl-L-homocysteine + (–)-bursehernin

For diagram of podophyllotoxin biosynthesis, click here

Glossary:

(–)-pluviatolide = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one
(–)-bursehernin = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(3,4-dimethoxyphenyl)methyl]oxolan-2-one

Other name(s):

OMT3 (gene name)

Systematic name:

S-adenosyl-L-methionine:(–)-pluviatolide 4-O-methyltransferase

Comments:

The enzyme, characterized from the plant Sinopodophyllum hexandrum, is involved in the biosynthetic pathway of podophyllotoxin, a non-alkaloid toxin lignan whose derivatives are important anticancer drugs.

Links to other databases:

References:

1.	Lau, W. and Sattely, E.S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349 (2015) 1224–1228. [DOI] [PMID: 26359402]

[EC 2.1.1.323 created 2016]

2.1.1.324

Accepted name:

dTDP-4-amino-2,3,4,6-tetradeoxy-D-glucose N,N-dimethyltransferase

Reaction:

2 S-adenosyl-L-methionine + dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose = 2 S-adenosyl-L-homocysteine + dTDP-α-D-forosamine (overall reaction)
(1a) S-adenosyl-L-methionine + dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose = S-adenosyl-L-homocysteine + dTDP-4-(methylamino)-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose
(1b) S-adenosyl-L-methionine + dTDP-4-(methylamino)-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose = S-adenosyl-L-homocysteine + dTDP-α-D-forosamine

For diagram of dTDP-forosamine biosynthesis, click here

Glossary:

dTDP-α-D-forosamine = dTDP-4-(dimethylamino)-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose

Other name(s):

SpnS; TDP-4-amino-2,3,6-trideoxy-D-glucose N,N-dimethyltransferase

Systematic name:

S-adenosyl-L-methionine:dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose N,N-dimethyltransferase

Comments:

The enzyme was isolated from the bacterium Saccharopolyspora spinosa, where it is involved in the biosynthesis of spinosyn A, an active ingredient of several commercial insecticides.

Links to other databases:

References:

1.	Hong, L., Zhao, Z., Melancon, C.E., 3rd, Zhang, H. and Liu, H.W. In vitro characterization of the enzymes involved in TDP-D-forosamine biosynthesis in the spinosyn pathway of Saccharopolyspora spinosa. J. Am. Chem. Soc. 130 (2008) 4954–4967. [DOI] [PMID: 18345667]

[EC 2.1.1.324 created 2016]

*EC

2.3.1.111

Accepted name:

mycocerosate synthase

Reaction:

(1) a long-chain acyl-[mycocerosic acid synthase] + 3 methylmalonyl-CoA + 6 NADPH + 6 H⁺ = a trimethylated-mycocerosoyl-[mycocerosate synthase] + 3 CoA + 3 CO₂ + 6 NADP⁺ + 3 H₂O
(2) a long-chain acyl-[mycocerosic acid synthase] + 4 methylmalonyl-CoA + 8 NADPH + 8 H⁺ = a tetramethylated-mycocerosoyl-[mycocerosate synthase] + 4 CoA + 4 CO₂ + 8 NADP⁺ + 4 H₂O

Glossary:

mycocerosic acid = a long-chain fatty acid with 3 or 4 methyl branches at positions 2,4,6 or 2,4,6,8, respectively. The carbon atoms bearing the methyl groups have the (R)-configuration.

Other name(s):

mas (gene name); mycocerosic acid synthase; acyl-CoA:methylmalonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing); long-chain acyl-CoA:methylmalonyl-CoA C-acyltransferase (mycocerosate-forming)

Systematic name:

long-chain acyl-[mycocerosic acid synthase]:methylmalonyl-CoA C-acyltransferase (mycocerosate-forming)

Comments:

The enzyme, characterized from mycobacteria, is loaded with a long-chain acyl moiety by EC 6.2.1.49, long-chain fatty acid adenylyltransferase FadD28, and elongates it by incorporation of three or four methylmalonyl (but not malonyl) residues, to form tri- or tetramethyl-branched fatty-acids, respectively, such as 2,4,6,8-tetramethyloctacosanoate (C₃₂-mycocerosate). Since the enzyme lacks a thioesterase domain, the product remains bound and requires additional enzyme(s) for removal. Even though the enzyme can accept C₆ to C₂₀ substrates in vitro, it prefers to act on C₁₄-C₂₀ substrates in vivo.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 95229-19-9

References:

1.	Rainwater, D.L. and Kollattukudy, P.E. Fatty acid biosynthesis in Mycobacterium tuberculosis var. bovis Bacillus* Calmette-Guérin. Purification and characterization of a novel fatty acid synthase, mycocerosic acid synthase, which elongates n-fatty acyl-CoA with methylmalonyl-CoA. J. Biol. Chem.* 260 (1985) 616–623. [PMID: 3880746]
2.	Mathur, M. and Kolattukudy, P.E. Molecular cloning and sequencing of the gene for mycocerosic acid synthase, a novel fatty acid elongating multifunctional enzyme, from Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guerin. J. Biol. Chem. 267 (1992) 19388–19395. [PMID: 1527058]
3.	Trivedi, O.A., Arora, P., Vats, A., Ansari, M.Z., Tickoo, R., Sridharan, V., Mohanty, D. and Gokhale, R.S. Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid. Mol. Cell 17 (2005) 631–643. [DOI] [PMID: 15749014]
4.	Menendez-Bravo, S., Comba, S., Sabatini, M., Arabolaza, A. and Gramajo, H. Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli. Metab. Eng. 24 (2014) 97–106. [DOI] [PMID: 24831705]

[EC 2.3.1.111 created 1989, modified 2016, modified 2017]

*EC

2.3.1.181

Accepted name:

lipoyl(octanoyl) transferase

Reaction:

an octanoyl-[acyl-carrier protein] + a protein = a protein N⁶-(octanoyl)lysine + an [acyl-carrier protein]

Glossary:

lipoyl group

Other name(s):

LipB; lipoyl (octanoyl)-[acyl-carrier-protein]-protein N-lipoyltransferase; lipoyl (octanoyl)-acyl carrier protein:protein transferase; lipoate/octanoate transferase; lipoyltransferase; octanoyl-[acyl carrier protein]-protein N-octanoyltransferase; lipoyl(octanoyl)transferase; octanoyl-[acyl-carrier-protein]:protein N-octanoyltransferase

Systematic name:

octanoyl-[acyl-carrier protein]:protein N-octanoyltransferase

Comments:

This is the first committed step in the biosynthesis of lipoyl cofactor. Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E₂ domain), 2-oxoglutarate dehydrogenase (E₂ domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [2,3]. Lipoyl-ACP can also act as a substrate [4] although octanoyl-ACP is likely to be the true substrate [6]. The other enzyme involved in the biosynthesis of lipoyl cofactor is EC 2.8.1.8, lipoyl synthase. An alternative lipoylation pathway involves EC 6.3.1.20, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues).

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, PDB, CAS registry number: 392687-64-8

References:

1.	Nesbitt, N.M., Baleanu-Gogonea, C., Cicchillo, R.M., Goodson, K., Iwig, D.F., Broadwater, J.A., Haas, J.A., Fox, B.G. and Booker, S.J. Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. Protein Expr. Purif. 39 (2005) 269–282. [DOI] [PMID: 15642479]
2.	Vanden Boom, T.J., Reed, K.E. and Cronan, J.E., Jr. Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. J. Bacteriol. 173 (1991) 6411–6420. [DOI] [PMID: 1655709]
3.	Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903–17906. [DOI] [PMID: 9218413]
4.	Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293–1302. [DOI] [PMID: 14700636]
5.	Wada, M., Yasuno, R., Jordan, S.W., Cronan, J.E., Jr. and Wada, H. Lipoic acid metabolism in Arabidopsis thaliana: cloning and characterization of a cDNA encoding lipoyltransferase. Plant Cell Physiol. 42 (2001) 650–656. [PMID: 11427685]
6.	Perham, R.N. Swinging arms and swinging domains in multifunctional enzymes: catalytic machines for multistep reactions. Annu. Rev. Biochem. 69 (2000) 961–1004. [DOI] [PMID: 10966480]

[EC 2.3.1.181 created 2006, modified 2016]

*EC

2.4.1.302

Accepted name:

L-demethylnoviosyl transferase

Reaction:

dTDP-4-O-demethyl-β-L-noviose + novobiocic acid = dTDP + demethyldecarbamoyl novobiocin

For diagram of novobiocin biosynthesis, click here

Glossary:

novobiocic acid = N-(2,7-dihydroxy-8-methyl-4-oxo-4H-chromen-3-yl)-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide
dTDP-4-O-demethyl-β-L-noviose = dTDP-6-deoxy-5-methyl-β-L-altropyranose = dTDP-(2S,3R,4R,5R)-6,6-dimethyltetrahydro-2H-pyran-2,3,4,5-tetraol
demethyldecarbamoyl novobiocin = N-{7-[(6-deoxy-5-methyl-β-D-gulopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide

Other name(s):

novM (gene name); dTDP-β-L-noviose:novobiocic acid 7-O-noviosyltransferase; L-noviosyl transferase

Systematic name:

dTDP-4-O-demethyl-β-L-noviose:novobiocic acid 7-O-[4-O-demethyl-L-noviosyl]transferase

Comments:

The enzyme is involved in the biosynthesis of the aminocoumarin antibiotic, novobiocin.

Links to other databases:

References:

1.	Freel Meyers, C.L., Oberthur, M., Anderson, J.W., Kahne, D. and Walsh, C.T. Initial characterization of novobiocic acid noviosyl transferase activity of NovM in biosynthesis of the antibiotic novobiocin. Biochemistry 42 (2003) 4179–4189. [DOI] [PMID: 12680772]
2.	Albermann, C., Soriano, A., Jiang, J., Vollmer, H., Biggins, J.B., Barton, W.A., Lesniak, J., Nikolov, D.B. and Thorson, J.S. Substrate specificity of NovM: implications for novobiocin biosynthesis and glycorandomization. Org. Lett. 5 (2003) 933–936. [DOI] [PMID: 12633109]

[EC 2.4.1.302 created 2013, modified 2016]

2.6.1.110

Accepted name:

dTDP-4-dehydro-2,3,6-trideoxy-D-glucose 4-aminotransferase

Reaction:

dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose + 2-oxoglutarate = dTDP-4-dehydro-2,3,6-trideoxy-α-D-hexopyranose + L-glutamate

For diagram of dTDP-forosamine biosynthesis, click here

Other name(s):

SpnR; TDP-4-keto-2,3,6-trideoxy-D-glucose 4-aminotransferase

Systematic name:

dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose:2-oxoglutarate aminotransferase

Comments:

A pyridoxal-phosphate protein. The enzyme, isolated from the bacterium Saccharopolyspora spinosa, participates in the biosynthesis of forosamine.

Links to other databases:

References:

1.	Hong, L., Zhao, Z., Melancon, C.E., 3rd, Zhang, H. and Liu, H.W. In vitro characterization of the enzymes involved in TDP-D-forosamine biosynthesis in the spinosyn pathway of Saccharopolyspora spinosa. J. Am. Chem. Soc. 130 (2008) 4954–4967. [DOI] [PMID: 18345667]

[EC 2.6.1.110 created 2016]

2.7.1.69

Transferred entry:

protein-N^π-phosphohistidine—sugar phosphotransferase, now covered by EC 2.7.1.191 protein-N^π-phosphohistidine—D-mannose phosphotransferase, EC 2.7.1.192 protein-N^π-phosphohistidine—N-acetylmuramate phosphotransferase, EC 2.7.1.193 protein-N^π-phosphohistidine—N-acetyl-D-glucosamine phosphotransferase, EC 2.7.1.194 protein-N^π-phosphohistidine—L-ascorbate phosphotransferase, EC 2.7.1.195 protein-N^π-phosphohistidine—2-O-α-mannosyl-D-glycerate phosphotransferase, EC 2.7.1.196 protein-N^π-phosphohistidine—N,N′-diacetylchitobiose phosphotransferase, EC 2.7.1.197 protein-N^π-phosphohistidine—D-mannitol phosphotransferase, EC 2.7.1.198 protein-N^π-phosphohistidine—D-sorbitol phosphotransferase, EC 2.7.1.199 protein-N^π-phosphohistidine—D-glucose phosphotransferase, EC 2.7.1.200 protein-N^π-phosphohistidine—galactitol phosphotransferase, EC 2.7.1.201 protein-N^π-phosphohistidine—trehalose phosphotransferase, EC 2.7.1.202 protein-N^π-phosphohistidine—D-fructose phosphotransferase, EC 2.7.1.203 protein-N^π-phosphohistidine—D-glucosaminate phosphotransferase, EC 2.7.1.204 protein-N^π-phosphohistidine—D-galactose phosphotransferase, EC 2.7.1.205 protein-N^π-phosphohistidine—cellobiose phosphotransferase, EC 2.7.1.206 protein-N^π-phosphohistidine—L-sorbose phosphotransferase, EC 2.7.1.207 protein-N^π-phosphohistidine—lactose phosphotransferase and EC 2.7.1.208 protein-N^π-phosphohistidine—maltose phosphotransferase.

[EC 2.7.1.69 created 1972, modified 2000, deleted 2016]

2.7.1.191

Accepted name:

protein-N^π-phosphohistidine—D-mannose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + D-mannose_{[side 1]} = [protein]-L-histidine + D-mannose 6-phosphate_{[side 2]}

Other name(s):

manXYZ (gene names); mannose PTS permease; EII^Man; Enzyme II^Man

Systematic name:

protein-N^π-phospho-L-histidine:D-mannose N^π-phosphotransferase

Comments:

This enzyme is a component (known as enzyme II) of a phosphoenolpyruvate (PEP)-dependent, sugar transporting phosphotransferase system (PTS). The system, which is found only in prokaryotes, simultaneously transports its substrate from the periplasm or extracellular space into the cytoplasm and phosphorylates it. The phosphate donor, which is shared among the different systems, is a phospho-carrier protein of low molecular mass that has been phosphorylated by EC 2.7.3.9 (phosphoenolpyruvate—protein phosphotransferase). Enzyme II, on the other hand, is specific for a particular substrate, although in some cases alternative substrates can be transported with lower efficiency. The reaction involves a successive transfer of the phosphate group to several amino acids within the enzyme before the final transfer to the substrate.

Links to other databases:

References:

1.	Erni, B. and Zanolari, B. The mannose-permease of the bacterial phosphotransferase system. Gene cloning and purification of the enzyme IIMan/IIIMan complex of Escherichia coli. J. Biol. Chem. 260 (1985) 15495–15503. [PMID: 2999119]
2.	Williams, N., Fox, D.K., Shea, C. and Roseman, S. Pel, the protein that permits lambda DNA penetration of Escherichia coli, is encoded by a gene in ptsM and is required for mannose utilization by the phosphotransferase system. Proc. Natl. Acad. Sci. USA 83 (1986) 8934–8938. [DOI] [PMID: 2947241]
3.	Erni, B., Zanolari, B. and Kocher, H.P. The mannose permease of Escherichia coli consists of three different proteins. Amino acid sequence and function in sugar transport, sugar phosphorylation, and penetration of phage lambda DNA. J. Biol. Chem. 262 (1987) 5238–5247. [PMID: 2951378]
4.	Stolz, B., Huber, M., Markovic-Housley, Z. and Erni, B. The mannose transporter of Escherichia coli. Structure and function of the IIABMan subunit. J. Biol. Chem. 268 (1993) 27094–27099. [PMID: 8262947]
5.	Rhiel, E., Flukiger, K., Wehrli, C. and Erni, B. The mannose transporter of Escherichia coli K12: oligomeric structure, and function of two conserved cysteines. Biol. Chem. Hoppe Seyler 375 (1994) 551–559. [PMID: 7811395]
6.	Huber, F. and Erni, B. Membrane topology of the mannose transporter of Escherichia coli K12. Eur. J. Biochem. 239 (1996) 810–817. [DOI] [PMID: 8774730]

[EC 2.7.1.191 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.191]

2.7.1.192

Accepted name:

protein-N^π-phosphohistidine—N-acetylmuramate phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + N-acetyl-D-muramate_{[side 1]} = [protein]-L-histidine + N-acetyl-D-muramate 6-phosphate_{[side 2]}

Other name(s):

murP (gene name); N-acetylmuramic acid PTS permease; EII^NAcMur; Enzyme II^NAcMur

Systematic name:

protein-N^π-phospho-L-histidine:N-acetyl-D-muramate N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Dahl, U., Jaeger, T., Nguyen, B.T., Sattler, J.M. and Mayer, C. Identification of a phosphotransferase system of Escherichia coli required for growth on N-acetylmuramic acid. J. Bacteriol. 186 (2004) 2385–2392. [DOI] [PMID: 15060041]

[EC 2.7.1.192 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.192]

2.7.1.193

Accepted name:

protein-N^π-phosphohistidine—N-acetyl-D-glucosamine phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + N-acetyl-D-glucosamine_{[side 1]} = [protein]-L-histidine + N-acetyl-D-glucosamine 6-phosphate_{[side 2]}

Other name(s):

nagE (gene name); N-acetyl-D-glucosamine PTS permease; EII^Nag; Enzyme II^Nag; EIICBA^Nag

Systematic name:

protein-N^π-phospho-L-histidine:N-acetyl-D-glucosamine N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	White, R.J. The role of the phosphoenolpyruvate phosphotransferase system in the transport of N-acetyl-D-glucosamine by Escherichia coli. Biochem. J. 118 (1970) 89–92. [PMID: 4919472]
2.	Rogers, M.J., Ohgi, T., Plumbridge, J. and Soll, D. Nucleotide sequences of the Escherichia coli nagE and nagB genes: the structural genes for the N-acetylglucosamine transport protein of the bacterial phosphoenolpyruvate: sugar phosphotransferase system and for glucosamine-6-phosphate deaminase. Gene 62 (1988) 197–207. [DOI] [PMID: 3284790]
3.	Peri, K.G. and Waygood, E.B. Sequence of cloned enzyme IIN-acetylglucosamine of the phosphoenolpyruvate:N-acetylglucosamine phosphotransferase system of Escherichia coli. Biochemistry 27 (1988) 6054–6061. [PMID: 3056518]
4.	Plumbridge, J. An alternative route for recycling of N-acetylglucosamine from peptidoglycan involves the N-acetylglucosamine phosphotransferase system in Escherichia coli. J. Bacteriol. 191 (2009) 5641–5647. [DOI] [PMID: 19617367]

[EC 2.7.1.193 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.193]

2.7.1.194

Accepted name:

protein-N^π-phosphohistidine—L-ascorbate phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + L-ascorbate_{[side 1]} = [protein]-L-histidine + L-ascorbate 6-phosphate_{[side 2]}

Other name(s):

ulaABC (gene names); L-ascorbate PTS permease; EII^Sga; Enzyme II^Sga; Enzyme II^Ula

Systematic name:

protein-N^π-phospho-L-histidine:L-ascorbate N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Zhang, Z., Aboulwafa, M., Smith, M.H. and Saier, M.H., Jr. The ascorbate transporter of Escherichia coli. J. Bacteriol. 185 (2003) 2243–2250. [DOI] [PMID: 12644495]
2.	Hvorup, R., Chang, A.B. and Saier, M.H., Jr. Bioinformatic analyses of the bacterial L-ascorbate phosphotransferase system permease family. J. Mol. Microbiol. Biotechnol. 6 (2003) 191–205. [DOI] [PMID: 15153772]
3.	Luo, P., Yu, X., Wang, W., Fan, S., Li, X. and Wang, J. Crystal structure of a phosphorylation-coupled vitamin C transporter. Nat. Struct. Mol. Biol. 22 (2015) 238–241. [DOI] [PMID: 25686089]

[EC 2.7.1.194 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.194]

2.7.1.195

Accepted name:

protein-N^π-phosphohistidine—2-O-α-mannosyl-D-glycerate phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + 2-O-(α-D-mannopyranosyl)-D-glycerate _{[side 1]} = [protein]-L-histidine + 2-O-(6-phospho-α-D-mannopyranosyl)-D-glycerate _{[side 2]}

Other name(s):

mngA (gene names); 2-O-α-mannosyl-D-glycerate PTS permease; EII^MngA; Enzyme II^MngA; Enzyme II^HrsA; EII^{mannosylglycerate}; Frx

Systematic name:

protein-N^π-phospho-L-histidine:2-O-α-mannopyranosyl-D-glycerate N^π-phosphotransferase

Comments:

Links to other databases:

References:

Sampaio, M.M., Chevance, F., Dippel, R., Eppler, T., Schlegel, A., Boos, W., Lu, Y.J. and Rock, C.O. Phosphotransferase-mediated transport of the osmolyte 2-O-α-mannosyl-D-glycerate in Escherichia coli occurs by the product of the mngA (hrsA) gene and is regulated by the mngR (farR) gene product acting as repressor. J. Biol. Chem. 279 (2004) 5537–5548. [DOI] [PMID: 14645248]

[EC 2.7.1.195 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.195]

2.7.1.196

Accepted name:

protein-N^π-phosphohistidine—N,N′-diacetylchitobiose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + N,N′-diacetylchitobiose_{[side 1]} = [protein]-L-histidine + N,N′-diacetylchitobiose 6′-phosphate_{[side 2]}

Other name(s):

chbABC (gene names); N,N′-diacetylchitobiose PTS permease; chitobiose PTS permease; EII^cel; EII^chb; Enzyme II^cel; Enzyme II^chb

Systematic name:

protein-N^π-phospho-L-histidine:N,N′-diacetylchitobiose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Keyhani, N.O., Wang, L.X., Lee, Y.C. and Roseman, S. The chitin disaccharide, N,N′-diacetylchitobiose, is catabolized by Escherichia coli and is transported/phosphorylated by the phosphoenolpyruvate:glycose phosphotransferase system. J. Biol. Chem. 275 (2000) 33084–33090. [DOI] [PMID: 10913117]
2.	Reizer, J., Reizer, A. and Saier, M.H., Jr. The cellobiose permease of Escherichia coli consists of three proteins and is homologous to the lactose permease of Staphylococcus aureus. Res. Microbiol. 141 (1990) 1061–1067. [DOI] [PMID: 2092358]
3.	Keyhani, N.O., Boudker, O. and Roseman, S. Isolation and characterization of IIAChb, a soluble protein of the enzyme II complex required for the transport/phosphorylation of N, N′-diacetylchitobiose in Escherichia coli. J. Biol. Chem. 275 (2000) 33091–33101. [DOI] [PMID: 10913118]
4.	Keyhani, N.O., Bacia, K. and Roseman, S. The transport/phosphorylation of N,N′-diacetylchitobiose in Escherichia coli. Characterization of phospho-IIB(Chb) and of a potential transition state analogue in the phosphotransfer reaction between the proteins IIA(Chb) AND IIB(Chb). J. Biol. Chem. 275 (2000) 33102–33109. [DOI] [PMID: 10913119]

[EC 2.7.1.196 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.196]

2.7.1.197

Accepted name:

protein-N^π-phosphohistidine—D-mannitol phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + D-mannitol_{[side 1]} = [protein]-L-histidine + D-mannitol 1-phosphate_{[side 2]}

Other name(s):

mtlA (gene name); D-mannitol PTS permease; EII^Mtl

Systematic name:

protein-N^π-phospho-L-histidine:D-mannitol N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Jacobson, G.R., Lee, C.A. and Saier, M.H., Jr. Purification of the mannitol-specific enzyme II of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system. J. Biol. Chem. 254 (1979) 249–252. [PMID: 368051]
2.	Jacobson, G.R., Tanney, L.E., Kelly, D.M., Palman, K.B. and Corn, S.B. Substrate and phospholipid specificity of the purified mannitol permease of Escherichia coli. J. Cell. Biochem. 23 (1983) 231–240. [DOI] [PMID: 6427236]
3.	Lee, C.A. and Saier, M.H., Jr. Mannitol-specific enzyme II of the bacterial phosphotransferase system. III. The nucleotide sequence of the permease gene. J. Biol. Chem. 258 (1983) 10761–10767. [PMID: 6309813]
4.	Elferink, M.G., Driessen, A.J. and Robillard, G.T. Functional reconstitution of the purified phosphoenolpyruvate-dependent mannitol-specific transport system of Escherichia coli in phospholipid vesicles: coupling between transport and phosphorylation. J. Bacteriol. 172 (1990) 7119–7125. [DOI] [PMID: 2123863]
5.	van Weeghel, R.P., Meyer, G., Pas, H.H., Keck, W. and Robillard, G.T. Cytoplasmic phosphorylating domain of the mannitol-specific transport protein of the phosphoenolpyruvate-dependent phosphotransferase system in Escherichia coli: overexpression, purification, and functional complementation with the mannitol binding domain. Biochemistry 30 (1991) 9478–9485. [PMID: 1909895]
6.	Boer, H., ten Hoeve-Duurkens, R.H. and Robillard, G.T. Relation between the oligomerization state and the transport and phosphorylation function of the Escherichia coli mannitol transport protein: interaction between mannitol-specific enzyme II monomers studied by complementation of inactive site-directed mutants. Biochemistry 35 (1996) 12901–12908. [DOI] [PMID: 8841134]

[EC 2.7.1.197 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.197]

2.7.1.198

Accepted name:

protein-N^π-phosphohistidine—D-sorbitol phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + D-sorbitol_{[side 1]} = [protein]-L-histidine + D-sorbitol 6-phosphate_{[side 2]}

Other name(s):

srlABE (gene names); D-sorbitol PTS permease; sorbitol PTS permease; glucitol PTS permease; EII^Gut; Enzyme II^Gut

Systematic name:

protein-N^π-phospho-L-histidine:D-sorbitol N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Lengeler, J. Nature and properties of hexitol transport systems in Escherichia coli. J. Bacteriol. 124 (1975) 39–47. [PMID: 1100608]
2.	Reizer, J., Mitchell, W.J., Minton, N., Brehm, J., Reizer, A. and Saier, M.H., Jr. Proposed topology of the glucitol permeases of Escherichia coli and Clostridium acetobutylicum. Curr. Microbiol. 33 (1996) 331–333. [PMID: 8875915]

[EC 2.7.1.198 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.198]

2.7.1.199

Accepted name:

protein-N^π-phosphohistidine—D-glucose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + D-glucose_{[side 1]} = [protein]-L-histidine + D-glucose 6-phosphate_{[side 2]}

Other name(s):

ptsG (gene name); D-glucose PTS permease; EII^Glc; Enzyme II^Glc

Systematic name:

protein-N^π-phospho-L-histidine:D-glucose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Stock, J.B., Waygood, E.B., Meadow, N.D., Postma, P.W. and Roseman, S. Sugar transport by the bacterial phosphotransferase system. The glucose receptors of the Salmonella typhimurium phosphotransferase system. J. Biol. Chem. 257 (1982) 14543–14552. [PMID: 6292227]
2.	Erni, B. and Zanolari, B. Glucose-permease of the bacterial phosphotransferase system. Gene cloning, overproduction, and amino acid sequence of enzyme IIGlc. J. Biol. Chem. 261 (1986) 16398–16403. [PMID: 3023349]

[EC 2.7.1.199 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.199]

2.7.1.200

Accepted name:

protein-N^π-phosphohistidine—galactitol phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + galactitol_{[side 1]} = [protein]-L-histidine + galactitol 1-phosphate_{[side 2]}

Other name(s):

gatABC (gene names); galactitol PTS permease; EII^Gat; Enzyme II^Gat

Systematic name:

protein-N^π-phospho-L-histidine:galactitol N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Lengeler, J. Nature and properties of hexitol transport systems in Escherichia coli. J. Bacteriol. 124 (1975) 39–47. [PMID: 1100608]
2.	Nobelmann, B. and Lengeler, J.W. Sequence of the gat operon for galactitol utilization from a wild-type strain EC3132 of Escherichia coli. Biochim. Biophys. Acta 1262 (1995) 69–72. [DOI] [PMID: 7772602]
3.	Nobelmann, B. and Lengeler, J.W. Molecular analysis of the gat genes from Escherichia coli and of their roles in galactitol transport and metabolism. J. Bacteriol. 178 (1996) 6790–6795. [DOI] [PMID: 8955298]

[EC 2.7.1.200 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.200]

2.7.1.201

Accepted name:

protein-N^π-phosphohistidine—trehalose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + α,α-trehalose_{[side 1]} = [protein]-L-histidine + α,α-trehalose 6-phosphate_{[side 2]}

Other name(s):

treB (gene name); trehalose PTS permease; EII^Tre; Enzyme II^Tre

Systematic name:

protein-N^π-phospho-L-histidine:α,α-trehalose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Boos, W., Ehmann, U., Forkl, H., Klein, W., Rimmele, M. and Postma, P. Trehalose transport and metabolism in Escherichia coli. J. Bacteriol. 172 (1990) 3450–3461. [DOI] [PMID: 2160944]
2.	Klein, W., Horlacher, R. and Boos, W. Molecular analysis of treB encoding the Escherichia coli enzyme II specific for trehalose. J. Bacteriol. 177 (1995) 4043–4052. [DOI] [PMID: 7608078]

[EC 2.7.1.201 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.201]

2.7.1.202

Accepted name:

protein-N^π-phosphohistidine—D-fructose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + D-fructose_{[side 1]} = [protein]-L-histidine + D-fructose 1-phosphate_{[side 2]}

Other name(s):

fruAB (gene names); fructose PTS permease; EII^Fru; Enzyme II^Fru

Systematic name:

protein-N^π-phospho-L-histidine:D-fructose N^π-phosphotransferase

Comments:

This enzyme is a component (known as enzyme II) of a phosphoenolpyruvate (PEP)-dependent, sugar transporting phosphotransferase system (PTS). The system, which is found only in prokaryotes, simultaneously transports its substrate from the periplasm or extracellular space into the cytoplasm and phosphorylates it. The phosphate donor, which is shared among the different systems, is usually a phospho-carrier protein of low molecular mass that has been phosphorylated by EC 2.7.3.9 (phosphoenolpyruvate—protein phosphotransferase). The enzyme from the bacterium Escherichia coli is an exception, since it is phosphorylated directly by EC 2.7.3.9. The reaction involves a successive transfer of the phosphate group to several amino acids within the enzyme before the final transfer to the substrate.

Links to other databases:

References:

1.	Waygood, E.B. Resolution of the phosphoenolpyruvate: fructose phosphotransferase system of Escherichia coli into two components: enzyme IIfructose and fructose-induced HPr-like protein (FPr). Can. J. Biochem. 58 (1980) 1144–1146. [PMID: 7006754]
2.	Kornberg, H. The roles of HPr and FPr in the utilization of fructose by Escherichia coli. FEBS Lett. 194 (1986) 12–15. [DOI] [PMID: 3510127]
3.	Geerse, R.H., Izzo, F. and Postma, P.W. The PEP: fructose phosphotransferase system in Salmonella typhimurium: FPr combines enzyme IIIFru and pseudo-HPr activities. Mol. Gen. Genet. 216 (1989) 517–525. [PMID: 2546043]
4.	Kornberg, H.L. and Lambourne, L.T. Role of the phosphoenolpyruvate-dependent fructose phosphotransferase system in the utilization of mannose by Escherichia coli. Proc Biol Sci 250 (1992) 51–55. [DOI] [PMID: 1361062]

[EC 2.7.1.202 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.202]

2.7.1.203

Accepted name:

protein-N^π-phosphohistidine—D-glucosaminate phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + 2-amino-2-deoxy-D-gluconate_{[side 1]} = [protein]-L-histidine + 2-amino-2-deoxy-D-gluconate 6-phosphate_{[side 2]}

Other name(s):

dgaABCD (gene names); 2-amino-2-deoxy-D-gluconate PTS permease

Systematic name:

protein-N^π-phospho-L-histidine:2-amino-2-deoxy-D-gluconate N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Miller, K.A., Phillips, R.S., Mrazek, J. and Hoover, T.R. Salmonella utilizes D-glucosaminate via a mannose family phosphotransferase system permease and associated enzymes. J. Bacteriol. 195 (2013) 4057–4066. [DOI] [PMID: 23836865]

[EC 2.7.1.203 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.203]

2.7.1.204

Accepted name:

protein-N^π-phosphohistidine—D-galactose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + D-galactose_{[side 1]} = [protein]-L-histidine + D-galactose 6-phosphate_{[side 2]}

Other name(s):

D-galactose PTS permease; EII^Gal; Enzyme II^Gal

Systematic name:

protein-N^π-phospho-L-histidine:D-galactose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Zeng, L., Martino, N.C. and Burne, R.A. Two gene clusters coordinate galactose and lactose metabolism in Streptococcus gordonii. Appl. Environ. Microbiol. 78 (2012) 5597–5605. [DOI] [PMID: 22660715]
2.	Zeng, L., Xue, P., Stanhope, M.J. and Burne, R.A. A galactose-specific sugar: phosphotransferase permease is prevalent in the non-core genome of Streptococcus mutans. Mol Oral Microbiol 28 (2013) 292–301. [DOI] [PMID: 23421335]

[EC 2.7.1.204 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.204]

2.7.1.205

Accepted name:

protein-N^π-phosphohistidine—cellobiose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + cellobiose_{[side 1]} = [protein]-L-histidine + 6-phospho-β-D-glucosyl-(1→4)-D-glucose_{[side 2]}

Other name(s):

celB (gene name); cellobiose PTS permease; EII^Cel; Enzyme II^Cel

Systematic name:

protein-N^π-phospho-L-histidine:cellobiose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Lai, X. and Ingram, L.O. Cloning and sequencing of a cellobiose phosphotransferase system operon from Bacillus stearothermophilus XL-65-6 and functional expression in Escherichia coli. J. Bacteriol. 175 (1993) 6441–6450. [DOI] [PMID: 8407820]
2.	Lai, X., Davis, F.C., Hespell, R.B. and Ingram, L.O. Cloning of cellobiose phosphoenolpyruvate-dependent phosphotransferase genes: functional expression in recombinant Escherichia coli and identification of a putative binding region for disaccharides. Appl. Environ. Microbiol. 63 (1997) 355–363. [PMID: 9023916]
3.	Stoll, R. and Goebel, W. The major PEP-phosphotransferase systems (PTSs) for glucose, mannose and cellobiose of Listeria monocytogenes, and their significance for extra- and intracellular growth. Microbiology 156 (2010) 1069–1083. [DOI] [PMID: 20056707]
4.	Wu, M.C., Chen, Y.C., Lin, T.L., Hsieh, P.F. and Wang, J.T. Cellobiose-specific phosphotransferase system of Klebsiella pneumoniae and its importance in biofilm formation and virulence. Infect. Immun. 80 (2012) 2464–2472. [DOI] [PMID: 22566508]

[EC 2.7.1.205 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.205]

2.7.1.206

Accepted name:

protein-N^π-phosphohistidine—L-sorbose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + L-sorbose_{[side 1]} = [protein]-L-histidine + L-sorbose 1-phosphate_{[side 2]}

Other name(s):

sorABFM (gene names); L-sorbose PTS permease; EII^Sor; Enzyme II^Sor

Systematic name:

protein-N^π-phospho-L-histidine:L-sorbose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Wehmeier, U.F., Wohrl, B.M. and Lengeler, J.W. Molecular analysis of the phosphoenolpyruvate-dependent L-sorbose: phosphotransferase system from Klebsiella pneumoniae and of its multidomain structure. Mol. Gen. Genet. 246 (1995) 610–618. [PMID: 7700234]
2.	Yebra, M.J., Veyrat, A., Santos, M.A. and Perez-Martinez, G. Genetics of L-sorbose transport and metabolism in Lactobacillus casei. J. Bacteriol. 182 (2000) 155–163. [DOI] [PMID: 10613875]

[EC 2.7.1.206 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.206]

2.7.1.207

Accepted name:

protein-N^π-phosphohistidine—lactose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + lactose_{[side 1]} = [protein]-L-histidine + lactose 6′-phosphate_{[side 2]}

Other name(s):

lacEF (gene names); lactose PTS permease; EII^Lac; Enzyme II^Lac

Systematic name:

protein-N^π-phospho-L-histidine:lactose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Hengstenberg, W. Solubilization of the membrane bound lactose specific component of the staphylococcal PEP dependant phosphotransferase system. FEBS Lett. 8 (1970) 277–280. [DOI] [PMID: 11947593]
2.	Vadeboncoeur, C. and Proulx, M. Lactose transport in Streptococcus mutans: isolation and characterization of factor IIIlac, a specific protein component of the phosphoenolpyruvate-lactose phosphotransferase system. Infect. Immun. 46 (1984) 213–219. [PMID: 6480107]
3.	Breidt, F., Jr., Hengstenberg, W., Finkeldei, U. and Stewart, G.C. Identification of the genes for the lactose-specific components of the phosphotransferase system in the lac operon of Staphylococcus aureus. J. Biol. Chem. 262 (1987) 16444–16449. [PMID: 2824493]
4.	De Vos, W.M., Boerrigter, I., Van Rooijen, R.J., Reiche, B., Hengstenberg, W. Characterization of the lactose-specific enzymes of the phosphotransferase system in Lactococcus lactis. J. Biol. Chem. 265 (1990) 22554–22560. [PMID: 2125052]
5.	Peters, D., Frank, R. and Hengstenberg, W. Lactose-specific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus aureus. Purification of the histidine-tagged transmembrane component IICBLac and its hydrophilic IIB domain by metal-affinity chromatography, and functional characterization. Eur. J. Biochem. 228 (1995) 798–804. [DOI] [PMID: 7737179]

[EC 2.7.1.207 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.207]

2.7.1.208

Accepted name:

protein-N^π-phosphohistidine—maltose phosphotransferase

Reaction:

[protein]-N^π-phospho-L-histidine + maltose_{[side 1]} = [protein]-L-histidine + maltose 6′-phosphate_{[side 2]}

Other name(s):

malT (gene name); maltose PTS permease; EII^Mal; Enzyme II^Mal

Systematic name:

protein-N^π-phospho-L-histidine:maltose N^π-phosphotransferase

Comments:

Links to other databases:

References:

1.	Robrish, S.A., Fales, H.M., Gentry-Weeks, C. and Thompson, J. Phosphoenolpyruvate-dependent maltose:phosphotransferase activity in Fusobacterium mortiferum ATCC 25557: specificity, inducibility, and product analysis. J. Bacteriol. 176 (1994) 3250–3256. [DOI] [PMID: 8195080]
2.	Webb, A.J., Homer, K.A. and Hosie, A.H. A phosphoenolpyruvate-dependent phosphotransferase system is the principal maltose transporter in Streptococcus mutans. J. Bacteriol. 189 (2007) 3322–3327. [DOI] [PMID: 17277067]

[EC 2.7.1.208 created 1972 as EC 2.7.1.69, part transferred 2016 to EC 2.7.1.208]

2.7.7.63

Transferred entry:

lipoate—protein ligase. Now EC 6.3.1.20, lipoate—protein ligase.

[EC 2.7.7.63 created 2006, deleted 2016]

2.7.7.90

Accepted name:

8-amino-3,8-dideoxy-manno-octulosonate cytidylyltransferase

Reaction:

CTP + 8-amino-3,8-dideoxy-α-D-manno-octulosonate = diphosphate + CMP-8-amino-3,8-dideoxy-α-D-manno-octulosonate

Other name(s):

kdsB (gene name, ambiguous)

Systematic name:

CTP:8-amino-3,8-dideoxy-α-D-manno-octulosonate cytidylyltransferase

Comments:

The enzyme, characterized from the bacterium Shewanella oneidensis MR-1, acts on the 8-aminated from of 3-deoxy-α-D-manno-octulosonate (Kdo). cf. EC 2.7.7.38, 3-deoxy-manno-octulosonate cytidylyltransferase.

Links to other databases:

References:

1.	Gattis, S.G., Chung, H.S., Trent, M.S. and Raetz, C.R. The origin of 8-amino-3,8-dideoxy-D-manno-octulosonic acid (Kdo8N) in the lipopolysaccharide of Shewanella oneidensis. J. Biol. Chem. 288 (2013) 9216–9225. [DOI] [PMID: 23413030]

[EC 2.7.7.90 created 2016]

3.1.1.99

Accepted name:

6-deoxy-6-sulfogluconolactonase

Reaction:

6-deoxy-6-sulfo-D-glucono-1,5-lactone + H₂O = 6-deoxy-6-sulfo-D-gluconate

For diagram of sulphoglycolysis of sulfoquinovose, click here

Other name(s):

SGL lactonase

Systematic name:

6-deoxy-6-sulfo-D-glucono-1,5-lactone lactonohydrolase

Comments:

The enzyme, characterized from the bacterium Pseudomonas putida SQ1, participates in a sulfoquinovose degradation pathway.

Links to other databases:

References:

1.	Felux, A.K., Spiteller, D., Klebensberger, J. and Schleheck, D. Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida SQ1. Proc. Natl. Acad. Sci. USA 112 (2015) E4298–E4305. [DOI] [PMID: 26195800]

[EC 3.1.1.99 created 2016]

3.1.3.99

Accepted name:

IMP-specific 5′-nucleotidase

Reaction:

IMP + H₂O = inosine + phosphate

Other name(s):

ISN1 (gene name)

Systematic name:

inosine 5′-phosphate phosphohydrolase

Comments:

The enzyme, isolated from the yeast Saccharomyces cerevisiae, is highly specific for inosine 5′-phosphate, and has no detectable activity with other purine and pyrimidine nucleotides. Requires divalent metals, such as Mg²⁺, Co²⁺ or Mn²⁺.

Links to other databases:

BRENDA, EXPASY, Gene, GTD, KEGG, PDB, CAS registry number: 9027-73-0

References:

1.	Itoh, R. Purification and some properties of an IMP-specific 5′-nucleotidase from yeast. Biochem. J. 298 (1994) 593–598. [PMID: 8141771]
2.	Itoh, R., Saint-Marc, C., Chaignepain, S., Katahira, R., Schmitter, J.M. and Daignan-Fornier, B. The yeast ISN1 (YOR155c) gene encodes a new type of IMP-specific 5′-nucleotidase. BMC Biochem. 4:4 (2003). [DOI] [PMID: 12735798]

[EC 3.1.3.99 created 2016]

3.1.3.100

Accepted name:

thiamine phosphate phosphatase

Reaction:

thiamine phosphate + H₂O = thiamine + phosphate

Systematic name:

thiamine phosphate phosphohydrolase

Comments:

The enzyme participates in the thiamine biosynthesis pathway in eukaryotes and a few prokaryotes. These organisms lack EC 2.7.4.16, thiamine-phosphate kinase, and need to convert thiamine phosphate to thiamine diphosphate, the active form of the vitamin, by first removing the phosphate group, followed by diphosphorylation by EC 2.7.6.2, thiamine diphosphokinase.

Links to other databases:

References:

1.	Sanemori, H., Egi, Y. and Kawasaki, T. Pathway of thiamine pyrophosphate synthesis in Micrococcus denitrificans. J. Bacteriol. 126 (1976) 1030–1036. [PMID: 181359]
2.	Komeda, Y., Tanaka, M. and Nishimune, T. A th-1 mutant of Arabidopsis thaliana is defective for a thiamin-phosphate-synthesizing enzyme: thiamin phosphate pyrophosphorylase. Plant Physiol. 88 (1988) 248–250. [PMID: 16666289]
3.	Schweingruber, A.M., Dlugonski, J., Edenharter, E. and Schweingruber, M.E. Thiamine in Schizosaccharomyces pombe: dephosphorylation, intracellular pool, biosynthesis and transport. Curr. Genet. 19 (1991) 249–254. [PMID: 1868574]
4.	Muller, I.B., Bergmann, B., Groves, M.R., Couto, I., Amaral, L., Begley, T.P., Walter, R.D. and Wrenger, C. The vitamin B₁ metabolism of Staphylococcus aureus is controlled at enzymatic and transcriptional levels. PLoS One 4:e7656 (2009). [DOI] [PMID: 19888457]
5.	Kolos, I.K. and Makarchikov, A.F. [Identification of thiamine monophosphate hydrolyzing enzymes in chicken liver] Ukr. Biochem. J. 86 (2014) 39–49. [PMID: 25816604] (in Russian)
6.	Mimura, M., Zallot, R., Niehaus, T.D., Hasnain, G., Gidda, S.K., Nguyen, T.N., Anderson, E.M., Mullen, R.T., Brown, G., Yakunin, A.F., de Crecy-Lagard, V., Gregory, J.F., 3rd, McCarty, D.R. and Hanson, A.D. Arabidopsis TH₂ encodes the orphan enzyme thiamin monophosphate phosphatase. Plant Cell 28 (2016) 2683–2696. [DOI] [PMID: 27677881]

[EC 3.1.3.100 created 2016]

3.2.1.196

Accepted name:

limit dextrin α-1,6-maltotetraose-hydrolase

Reaction:

Hydrolysis of (1→6)-α-D-glucosidic linkages to branches with degrees of polymerization of three or four glucose residues in limit dextrin.

Other name(s):

glgX (gene name); glycogen debranching enzyme (ambiguous)

Systematic name:

glycogen phosphorylase-limit dextrin maltotetraose-hydrolase

Comments:

This bacterial enzyme catalyses a reaction similar to EC 3.2.1.33, amylo-α-1,6-glucosidase (one of the activities of the eukaryotic glycogen debranching enzyme). However, while EC 3.2.1.33 removes single glucose residues linked by 1,6-α-linkage, and thus requires the additional activity of 4-α-glucanotransferase (EC 2.4.1.25) to act on limit dextrins formed by glycogen phosphorylase (EC 2.4.1.1), this enzyme removes maltotriose and maltotetraose chains that are attached by 1,6-α-linkage to the limit dextrin main chain, generating a debranched limit dextrin without a need for another enzyme.

Links to other databases:

References:

1.	Jeanningros, R., Creuzet-Sigal, N., Frixon, C. and Cattaneo, J. Purification and properties of a debranching enzyme from Escherichia coli. Biochim. Biophys. Acta 438 (1976) 186–199. [DOI] [PMID: 779849]
2.	Dauvillee, D., Kinderf, I.S., Li, Z., Kosar-Hashemi, B., Samuel, M.S., Rampling, L., Ball, S. and Morell, M.K. Role of the Escherichia coli glgX gene in glycogen metabolism. J. Bacteriol. 187 (2005) 1465–1473. [DOI] [PMID: 15687211]
3.	Song, H.N., Jung, T.Y., Park, J.T., Park, B.C., Myung, P.K., Boos, W., Woo, E.J. and Park, K.H. Structural rationale for the short branched substrate specificity of the glycogen debranching enzyme GlgX. Proteins 78 (2010) 1847–1855. [DOI] [PMID: 20187119]

[EC 3.2.1.196 created 2016]

3.7.1.23

Accepted name:

maleylpyruvate hydrolase

Reaction:

3-maleylpyruvate + H₂O = maleate + pyruvate

Glossary:

3-maleylpyruvate = (2Z)-4,6-dioxohept-2-enedioate

Other name(s):

hbzF (gene name)

Systematic name:

(2Z)-4,6-dioxohept-2-enedioate acylhydrolase

Comments:

The enzyme, characterized from the bacterium Pseudomonas alcaligenes NCIMB 9867, catalyses the hydrolysis of 3-maleylpyruvate, the ring-cleavage product of gentisate. The enzyme can also act on a number of maleylpyruvate derivatives, such as (2E)-2-methyl-4,6-dioxohept-2-enedioate and (2E)-3-methyl-4,6-dioxohept-2-enedioate. Activated by Mn²⁺. May be identical to EC 3.7.1.5, acylpyruvate hydrolase.

Links to other databases:

References:

1.	Hopper, D.J., Chapman, P.J. and Dagley, S. The enzymic degradation of alkyl-substituted gentisates, maleates and malates. Biochem. J. 122 (1971) 29–40. [PMID: 5124802]
2.	Bayly, R.C., Chapman, P.J., Dagley, S. and Di Berardino, D. Purification and some properties of maleylpyruvate hydrolase and fumarylpyruvate hydrolase from Pseudomonas alcaligenes. J. Bacteriol. 143 (1980) 70–77. [PMID: 7400101]
3.	Liu, K., Liu, T.T. and Zhou, N.Y. HbzF catalyzes direct hydrolysis of maleylpyruvate in the gentisate pathway of Pseudomonas alcaligenes NCIMB 9867. Appl. Environ. Microbiol. 79 (2013) 1044–1047. [DOI] [PMID: 23204427]

[EC 3.7.1.23 created 2016]

3.9.1.3

Accepted name:

phosphohistidine phosphatase

Reaction:

a [protein]-N-phospho-L-histidine + H₂O = a [protein]-L-histidine + phosphate

Other name(s):

PHPT1 (gene name); protein histidine phosphatase; PHP

Systematic name:

[protein]-N-phospho-L-histidine phosphohydrolase

Comments:

This eukaryotic enzyme dephosphorylates phosphorylated histidine residues within proteins and peptides. The enzyme acts on phosphate groups attached to both the pros- and tele-nitrogen atoms, but the pros- position is somewhat preferred (by a factor of two at the most) [4]. The substrate specificity depends on the amino acid sequence or structural context of the phosphohistidine in a phosphoprotein. The enzyme is also active on free phosphoramidate [1,4] and peptide-bound phospholysine [5].

Links to other databases:

References:

1.	Ek, P., Pettersson, G., Ek, B., Gong, F., Li, J.P. and Zetterqvist, O. Identification and characterization of a mammalian 14-kDa phosphohistidine phosphatase. Eur. J. Biochem. 269 (2002) 5016–5023. [DOI] [PMID: 12383260]
2.	Klumpp, S., Hermesmeier, J., Selke, D., Baumeister, R., Kellner, R. and Krieglstein, J. Protein histidine phosphatase: a novel enzyme with potency for neuronal signaling. J Cereb Blood Flow Metab 22 (2002) 1420–1424. [DOI] [PMID: 12468887]
3.	Baumer, N., Maurer, A., Krieglstein, J. and Klumpp, S. Expression of protein histidine phosphatase in Escherichia coli, purification, and determination of enzyme activity. Methods Mol. Biol. 365 (2007) 247–260. [DOI] [PMID: 17200567]
4.	Attwood, P.V., Ludwig, K., Bergander, K., Besant, P.G., Adina-Zada, A., Krieglstein, J. and Klumpp, S. Chemical phosphorylation of histidine-containing peptides based on the sequence of histone H4 and their dephosphorylation by protein histidine phosphatase. Biochim. Biophys. Acta 1804 (2010) 199–205. [DOI] [PMID: 19836471]
5.	Ek, P., Ek, B. and Zetterqvist, O. Phosphohistidine phosphatase 1 (PHPT1) also dephosphorylates phospholysine of chemically phosphorylated histone H1 and polylysine. Ups J Med Sci 120 (2015) 20–27. [DOI] [PMID: 25574816]

[EC 3.9.1.3 created 2016]

4.1.2.58

Accepted name:

2-dehydro-3,6-dideoxy-6-sulfogluconate aldolase

Reaction:

2-dehydro-3,6-dideoxy-6-sulfo-D-gluconate = (2S)-3-sulfolactaldehyde + pyruvate

Glossary:

(2S)-3-sulfolactaldehyde = (2S)-2-hydroxy-3-oxopropane-1-sulfonate

Other name(s):

KDSG aldolase

Systematic name:

2-dehydro-3,6-dideoxy-6-sulfo-D-gluconate (2S)-3-sulfolactaldehyde-lyase (pyruvate-forming)

Comments:

The enzyme, characterized from the bacterium Pseudomonas putida SQ1, participates in a sulfoquinovose degradation pathway.

Links to other databases:

References:

1.	Felux, A.K., Spiteller, D., Klebensberger, J. and Schleheck, D. Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida SQ1. Proc. Natl. Acad. Sci. USA 112 (2015) E4298–E4305. [DOI] [PMID: 26195800]

[EC 4.1.2.58 created 2016]

4.2.1.162

Accepted name:

6-deoxy-6-sulfo-D-gluconate dehydratase

Reaction:

6-deoxy-6-sulfo-D-gluconate = 2-dehydro-3,6-dideoxy-6-sulfo-D-gluconate + H₂O

For diagram of sulphoglycolysis of sulfoquinovose, click here

Other name(s):

SG dehydratase

Systematic name:

6-deoxy-6-sulfo-D-gluconate hydro-lyase (2-dehydro-3,6-dideoxy-6-sulfo-D-gluconate-forming)

Comments:

The enzyme, characterized from the bacterium Pseudomonas putida SQ1, participates in a sulfoquinovose degradation pathway.

Links to other databases:

References:

1.	Felux, A.K., Spiteller, D., Klebensberger, J. and Schleheck, D. Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida SQ1. Proc. Natl. Acad. Sci. USA 112 (2015) E4298–E4305. [DOI] [PMID: 26195800]

[EC 4.2.1.162 created 2016]

4.2.1.163

Accepted name:

2-oxo-hept-4-ene-1,7-dioate hydratase

Reaction:

(4Z)-2-oxohept-4-enedioate + H₂O = (4S)-4-hydroxy-2-oxoheptanedioate

Other name(s):

HpcG

Systematic name:

(4S)-4-hydroxy-2-oxoheptanedioate hydro-lyase [(4Z)-2-oxohept-4-enedioate-forming]

Comments:

Requires Mg²⁺ [2]. Part of a 4-hydroxyphenylacetate degradation pathway in Escherichia coli C.

Links to other databases:

References:

1.	Burks, E.A., Johnson, W.H., Jr. and Whitman, C.P. Stereochemical and isotopic labeling studies of 2-oxo-hept-4-ene-1,7-dioate hydratase: evidence for an enzyme-catalyzed ketonization step in the hydration reaction. J. Am. Chem. Soc. 120 (1998) 7665–7675.
2.	Izumi, A., Rea, D., Adachi, T., Unzai, S., Park, S.Y., Roper, D.I. and Tame, J.R. Structure and mechanism of HpcG, a hydratase in the homoprotocatechuate degradation pathway of Escherichia coli. J. Mol. Biol. 370 (2007) 899–911. [DOI] [PMID: 17559873]

[EC 4.2.1.163 created 2016]

4.2.99.23

Accepted name:

tuliposide B-converting enzyme

Reaction:

6-tuliposide B = tulipalin B + D-glucose

Glossary:

6-tuliposide B = 6-O-[(3S)-3,4-dihydroxy-2-methylenebutanoyl]-D-glucose
tulipalin B = (4S)-4-hydroxy-3-methylideneoxolan-2-one

Systematic name:

6-tuliposide B D-glucose-lyase (tulipalin B-forming)

Comments:

The enzyme, characterized from pollen of the plant Tulipa gesneriana (tulip), catalyses the intramolecular transesterification of 6-tuliposide B to form the antibiotic aglycon tulipalin B as a sole product. It does not catalyse the hydrolysis of 6-tuliposide B to form a hydroxy acid. The enzyme has marginal activity with 6-tuliposide A. cf. EC 4.2.99.22, tuliposide A-converting enzyme.

Links to other databases: