The Enzyme Database

Displaying entries 101-150 of 241.

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EC 1.14.11.60     
Accepted name: scopoletin 8-hydroxylase
Reaction: scopoletin + 2-oxoglutarate + O2 = fraxetin + succinate + CO2
Glossary: fraxetin = 7,8-dihydroxy-6-methoxy-2H-chromen-2-one
scopoletin = 7-hydroxy-6-methoxy-2H-chromen-2-one
Other name(s): S8H (gene name)
Systematic name: scopoletin,2-oxoglutarate:oxygen oxidoreductase (8-hydroxylating)
Comments: Requires iron(II) and ascorbate. A protein involved in biosynthesis of iron(III)-chelating coumarins in higher plants.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Siwinska, J., Siatkowska, K., Olry, A., Grosjean, J., Hehn, A., Bourgaud, F., Meharg, A.A., Carey, M., Lojkowska, E. and Ihnatowicz, A. Scopoletin 8-hydroxylase: a novel enzyme involved in coumarin biosynthesis and iron-deficiency responses in Arabidopsis. J. Exp. Bot. 69 (2018) 1735–1748. [PMID: 29361149]
2.  Rajniak, J., Giehl, R.FH., Chang, E., Murgia, I., von Wiren, N. and Sattely, E.S. Biosynthesis of redox-active metabolites in response to iron deficiency in plants. Nat. Chem. Biol. 14 (2018) 442–450. [PMID: 29581584]
[EC 1.14.11.60 created 2018]
 
 
EC 1.14.11.61     
Accepted name: feruloyl-CoA 6-hydroxylase
Reaction: trans-feruloyl-CoA + 2-oxoglutarate + O2 = trans-6-hydroxyferuloyl-CoA + succinate + CO2
Glossary: trans-feruloyl-CoA = 4-hydroxy-3-methoxycinnamoyl-CoA = (E)-3-(4-hydroxy-3-methoxyphenyl)propenoyl-CoA
Systematic name: feruloyl-CoA,2-oxoglutarate:oxygen oxidoreductase (6-hydroxylating)
Comments: Requires iron(II) and ascorbate. The product spontaneously undergoes trans-cis isomerization and lactonization to form scopoletin, liberating CoA in the process. The enzymes from the plants Ruta graveolens and Ipomoea batatas also act on trans-4-coumaroyl-CoA. cf. EC 1.14.11.62, trans-4-coumaroyl-CoA 2-hydroxylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Kai, K., Mizutani, M., Kawamura, N., Yamamoto, R., Tamai, M., Yamaguchi, H., Sakata, K. and Shimizu, B. Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana. Plant J. 55 (2008) 989–999. [PMID: 18547395]
2.  Bayoumi, S.A., Rowan, M.G., Blagbrough, I.S. and Beeching, J.R. Biosynthesis of scopoletin and scopolin in cassava roots during post-harvest physiological deterioration: the E-Z-isomerisation stage. Phytochemistry 69 (2008) 2928–2936. [PMID: 19004461]
3.  Vialart, G., Hehn, A., Olry, A., Ito, K., Krieger, C., Larbat, R., Paris, C., Shimizu, B., Sugimoto, Y., Mizutani, M. and Bourgaud, F. A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2′-hydroxylase activity (C2′H): a missing step in the synthesis of umbelliferone in plants. Plant J. 70 (2012) 460–470. [DOI] [PMID: 22168819]
4.  Matsumoto, S., Mizutani, M., Sakata, K. and Shimizu, B. Molecular cloning and functional analysis of the ortho-hydroxylases of p-coumaroyl coenzyme A/feruloyl coenzyme A involved in formation of umbelliferone and scopoletin in sweet potato, Ipomoea batatas (L.) Lam. Phytochemistry 74 (2012) 49–57. [PMID: 22169019]
[EC 1.14.11.61 created 2019]
 
 
EC 1.14.11.62     
Accepted name: trans-4-coumaroyl-CoA 2-hydroxylase
Reaction: trans-4-coumaroyl-CoA + 2-oxoglutarate + O2 = 2,4-dihydroxycinnamoyl-CoA + succinate + CO2
Glossary: trans-4-coumaroyl-CoA = (2E)-3-(4-hydroxyphenyl)prop-2-enoyl-CoA
2,4-dihydroxycinnamoyl-CoA = (2E)-3-(2,4-dihydroxyphenyl)prop-2-enoyl-CoA
umbelliferone = 7-hydroxycoumarin
Other name(s): Diox4 (gene name); C2′H (gene name)
Systematic name: (2E)-3-(4-hydroxyphenyl)prop-2-enoyl-CoA,2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating)
Comments: Requires iron(II) and ascorbate. The product spontaneously undergoes trans-cis isomerization followed by lactonization and cyclization, liberating CoA and forming umbelliferone. The enzymes from the plants Ruta graveolens and Ipomoea batatas also act on trans-feruloyl-CoA (cf. EC 1.14.11.61, feruloyl-CoA 6-hydroxylase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Vialart, G., Hehn, A., Olry, A., Ito, K., Krieger, C., Larbat, R., Paris, C., Shimizu, B., Sugimoto, Y., Mizutani, M. and Bourgaud, F. A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2′-hydroxylase activity (C2′H): a missing step in the synthesis of umbelliferone in plants. Plant J. 70 (2012) 460–470. [DOI] [PMID: 22168819]
2.  Matsumoto, S., Mizutani, M., Sakata, K. and Shimizu, B. Molecular cloning and functional analysis of the ortho-hydroxylases of p-coumaroyl coenzyme A/feruloyl coenzyme A involved in formation of umbelliferone and scopoletin in sweet potato, Ipomoea batatas (L.) Lam. Phytochemistry 74 (2012) 49–57. [PMID: 22169019]
[EC 1.14.11.62 created 2019]
 
 
EC 1.14.11.63     
Accepted name: peptidyl-lysine (3S)-dioxygenase
Reaction: a [protein]-L-lysine + 2-oxoglutarate + O2 = a [protein]-(3S)-3-hydroxy-L-lysine + succinate + CO2
Other name(s): JMJD7 (gene name); Jumonji domain-containing protein 7; JmjC domain-containing protein 7
Systematic name: [protein]-L-lysine,2-oxoglutarate:oxygen oxidoreductase (3S-hydroxylating)
Comments: Requires iron(II). The enzyme acts on specific lysine residues in its substrates, and is stereo-specific. The enzyme encoded by the human JMJD7 gene acts specifically on two related members of the translation factor family of GTPases, DRG1 and DRG2.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Markolovic, S., Zhuang, Q., Wilkins, S.E., Eaton, C.D., Abboud, M.I., Katz, M.J., McNeil, H.E., Lesniak, R.K., Hall, C., Struwe, W.B., Konietzny, R., Davis, S., Yang, M., Ge, W., Benesch, J.LP., Kessler, B.M., Ratcliffe, P.J., Cockman, M.E., Fischer, R., Wappner, P., Chowdhury, R., Coleman, M.L. and Schofield, C.J. The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases. Nat. Chem. Biol. 14 (2018) 688–695. [PMID: 29915238]
[EC 1.14.11.63 created 2019]
 
 
EC 1.14.11.64     
Accepted name: glutarate dioxygenase
Reaction: glutarate + 2-oxoglutarate + O2 = (S)-2-hydroxyglutarate + succinate + CO2
Other name(s): csiD (gene name)
Systematic name: glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming)
Comments: Requires iron(II). The enzyme, characterized from the bacteria Escherichia coli and Pseudomonas putida, participates in L-lysine degradation in many bacteria. It provides an alternative route for L-glutarate degradation that does not proceed via CoA-activated intermediates.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Knorr, S., Sinn, M., Galetskiy, D., Williams, R.M., Wang, C., Muller, N., Mayans, O., Schleheck, D. and Hartig, J.S. Widespread bacterial lysine degradation proceeding via glutarate and L-2-hydroxyglutarate. Nat. Commun. 9:5071 (2018). [PMID: 30498244]
2.  Zhang, M., Gao, C., Guo, X., Guo, S., Kang, Z., Xiao, D., Yan, J., Tao, F., Zhang, W., Dong, W., Liu, P., Yang, C., Ma, C. and Xu, P. Increased glutarate production by blocking the glutaryl-CoA dehydrogenation pathway and a catabolic pathway involving L-2-hydroxyglutarate. Nat. Commun. 9:2114 (2018). [PMID: 29844506]
[EC 1.14.11.64 created 2019]
 
 
EC 1.14.11.65     
Accepted name: [histone H3]-dimethyl-L-lysine9 demethylase
Reaction: a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-L-lysine9 + succinate + formaldehyde + CO2
Other name(s): KDM3A (gene name); KDM3B (gene name); JMJD1A (gene name); JMJD1B (gene name); JHDM2A (gene name); JHDM2B (gene name); KDM7B (gene name); PHF8 (gene name); HR (gene name)
Systematic name: [histone H3]-N6,N6-dimethyl-L-lysine9,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the di- and mono-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.66, [histone H3]-trimethyl-L-lysine9 demethylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Yamane, K., Toumazou, C., Tsukada, Y., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation by androgen receptor. Cell 125 (2006) 483–495. [PMID: 16603237]
2.  Loh, Y.H., Zhang, W., Chen, X., George, J. and Ng, H.H. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 21 (2007) 2545–2557. [PMID: 17938240]
3.  Feng, W., Yonezawa, M., Ye, J., Jenuwein, T. and Grummt, I. PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. Nat. Struct. Mol. Biol. 17 (2010) 445–450. [PMID: 20208542]
4.  Kuroki, S., Matoba, S., Akiyoshi, M., Matsumura, Y., Miyachi, H., Mise, N., Abe, K., Ogura, A., Wilhelm, D., Koopman, P., Nozaki, M., Kanai, Y., Shinkai, Y. and Tachibana, M. Epigenetic regulation of mouse sex determination by the histone demethylase Jmjd1a. Science 341 (2013) 1106–1109. [PMID: 24009392]
5.  Liu, L., Kim, H., Casta, A., Kobayashi, Y., Shapiro, L.S. and Christiano, A.M. Hairless is a histone H3K9 demethylase. FASEB J. 28 (2014) 1534–1542. [PMID: 24334705]
[EC 1.14.11.65 created 2019]
 
 
EC 1.14.11.66     
Accepted name: [histone H3]-trimethyl-L-lysine9 demethylase
Reaction: a [histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-N6-methyl-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
Other name(s): KDM4A (gene name); KDM4B (gene name); KDM4C (gene name); KDM4D (gene name); JHDM3A (gene name); JMJD2 (gene name); JMJD2A (gene name); GASC1 (gene name)
Systematic name: [histone H3]-N6,N6,N6-trimethyl-L-lysine9,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.65, [histone H3]-dimethyl-L-lysine9 demethylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Cloos, P.A., Christensen, J., Agger, K., Maiolica, A., Rappsilber, J., Antal, T., Hansen, K.H. and Helin, K. The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3. Nature 442 (2006) 307–311. [PMID: 16732293]
2.  Fodor, B.D., Kubicek, S., Yonezawa, M., O'Sullivan, R.J., Sengupta, R., Perez-Burgos, L., Opravil, S., Mechtler, K., Schotta, G. and Jenuwein, T. Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes Dev. 20 (2006) 1557–1562. [PMID: 16738407]
3.  Klose, R.J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442 (2006) 312–316. [PMID: 16732292]
4.  Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G., Colaiacovo, M. and Shi, Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125 (2006) 467–481. [PMID: 16603238]
[EC 1.14.11.66 created 2019]
 
 
EC 1.14.11.67     
Accepted name: [histone H3]-trimethyl-L-lysine4 demethylase
Reaction: a [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 3 2-oxoglutarate + 3 O2 = a [histone H3]-L-lysine4 + 3 succinate + 3 formaldehyde + 3 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine4 + succinate + formaldehyde + CO2
(1c) a [histone H3]-N6-methyl-L-lysine4 + 2-oxoglutarate + O2 = a [histone H3]-L-lysine4 + succinate + formaldehyde + CO2
Other name(s): KDM5A (gene name); KDM5B (gene name); KDM5C (gene name); KDM5D (gene name); JARID1A (gene name)
Systematic name: [histone H3]-N6,N6,N6-trimethyl-L-lysine4,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 4 of histone H3 (H3K4). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri-, di-, and mono-methylated forms.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Seward, D.J., Cubberley, G., Kim, S., Schonewald, M., Zhang, L., Tripet, B. and Bentley, D.L. Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins. Nat. Struct. Mol. Biol. 14 (2007) 240–242. [PMID: 17310255]
2.  Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y. and Kaelin, W.G., Jr. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell 128 (2007) 889–900. [PMID: 17320163]
3.  Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M. and Shi, Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128 (2007) 1077–1088. [PMID: 17320160]
4.  Christensen, J., Agger, K., Cloos, P.A., Pasini, D., Rose, S., Sennels, L., Rappsilber, J., Hansen, K.H., Salcini, A.E. and Helin, K. RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell 128 (2007) 1063–1076. [PMID: 17320161]
[EC 1.14.11.67 created 2019]
 
 
EC 1.14.11.68     
Accepted name: [histone H3]-trimethyl-L-lysine27 demethylase
Reaction: a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-N6-methyl-L-lysine27 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine27 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine27 + succinate + formaldehyde + CO2
Other name(s): KDM6A (gene name); KDM6C (gene name); UTX (gene name); UTY (gene name); JMJD3 (gene name)
Systematic name: [histone H3]-N6,N6,N6-trimethyl-L-lysine27,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 27 of histone H3 (H3K27). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri- and di-methylated forms, but have no activity with the mono-methylated form.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  De Santa, F., Totaro, M.G., Prosperini, E., Notarbartolo, S., Testa, G. and Natoli, G. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell 130 (2007) 1083–1094. [PMID: 17825402]
2.  Hong, S., Cho, Y.W., Yu, L.R., Yu, H., Veenstra, T.D. and Ge, K. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc. Natl. Acad. Sci. USA 104 (2007) 18439–18444. [PMID: 18003914]
3.  Lan, F., Bayliss, P.E., Rinn, J.L., Whetstine, J.R., Wang, J.K., Chen, S., Iwase, S., Alpatov, R., Issaeva, I., Canaani, E., Roberts, T.M., Chang, H.Y. and Shi, Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449 (2007) 689–694. [PMID: 17851529]
4.  Lee, M.G., Villa, R., Trojer, P., Norman, J., Yan, K.P., Reinberg, D., Di Croce, L. and Shiekhattar, R. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318 (2007) 447–450. [PMID: 17761849]
5.  Xiang, Y., Zhu, Z., Han, G., Lin, H., Xu, L. and Chen, C.D. JMJD3 is a histone H3K27 demethylase. Cell Res. 17 (2007) 850–857. [PMID: 17923864]
[EC 1.14.11.68 created 2019]
 
 
EC 1.14.11.69     
Accepted name: [histone H3]-trimethyl-L-lysine36 demethylase
Reaction: a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-N6-methyl-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction)
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
Other name(s): KDM4A (gene name); KDM4B (gene name); RPH1 (gene name); JHDM3A (gene name); JHDM3B (gene name); JMJD2A (gene name); JMJD2B (gene name)
Systematic name: [histone H3]-N6,N6,N6-trimethyl-L-lysine36,2-oxoglutarate:oxygen oxidoreductase
Comments: Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys36 residues in the tail of the histone protein H3 (H3K36). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. Since trimethylation of H3K36 enhances transcription, this enzyme acts as a transcription repressor. The enzymes that possess this activity often also catalyse the activity of EC 1.14.11.66, [histone H3]-trimethyl-L-lysine9 demethylase. cf. EC 1.14.11.27, [histone H3]-dimethyl-L-lysine36 demethylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Whetstine, J.R., Nottke, A., Lan, F., Huarte, M., Smolikov, S., Chen, Z., Spooner, E., Li, E., Zhang, G., Colaiacovo, M. and Shi, Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125 (2006) 467–481. [PMID: 16603238]
2.  Klose, R.J., Yamane, K., Bae, Y., Zhang, D., Erdjument-Bromage, H., Tempst, P., Wong, J. and Zhang, Y. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442 (2006) 312–316. [PMID: 16732292]
3.  Kim, T. and Buratowski, S. Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation. J. Biol. Chem. 282 (2007) 20827–20835. [PMID: 17525156]
4.  Couture, J.F., Collazo, E., Ortiz-Tello, P.A., Brunzelle, J.S. and Trievel, R.C. Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase. Nat. Struct. Mol. Biol. 14 (2007) 689–695. [PMID: 17589523]
5.  Lin, C.H., Li, B., Swanson, S., Zhang, Y., Florens, L., Washburn, M.P., Abmayr, S.M. and Workman, J.L. Heterochromatin protein 1a stimulates histone H3 lysine 36 demethylation by the Drosophila KDM4A demethylase. Mol. Cell 32 (2008) 696–706. [PMID: 19061644]
6.  Colmenares, S.U., Swenson, J.M., Langley, S.A., Kennedy, C., Costes, S.V. and Karpen, G.H. Drosophila histone demethylase KDM4A has enzymatic and non-enzymatic roles in controlling heterochromatin integrity. Dev Cell 42 (2017) 156–169.e5. [PMID: 28743002]
[EC 1.14.11.69 created 2019]
 
 
EC 1.14.11.70     
Accepted name: 7-deoxycylindrospermopsin hydroxylase
Reaction: (1) 7-deoxycylindrospermopsin + 2-oxoglutarate + O2 = cylindrospermopsin + succinate + CO2
(2) 7-deoxycylindrospermopsin + 2-oxoglutarate + O2 = 7-epi-cylindrospermopsin + succinate + CO2
Glossary: cylindrospermopsin = (2aS,3R,4S,5aS,7R)-7-[(R)-(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)(hydroxy)methyl]-3-methyl-2a,3,4,5,5a,6,7,8-octahydro-2H-1,8,8b-triazaacenaphthylen-4-yl hydrogen sulfate
Other name(s): cyrI (gene name)
Systematic name: 7-deoxycylindrospermopsin,2-oxoglutarate:oxygen oxidoreductase (7-hydroxylating)
Comments: Requires iron(II). The enzyme, found in some cyanobacterial species, catalyses the last step in the biosynthesis of the toxins cylindrospermopsin and 7-epi-cylindrospermopsin. The ratio of the two products differs among different strains.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Mazmouz, R., Chapuis-Hugon, F., Pichon V., Mejean, A., and Ploux, O. The last step of the biosynthesis of the cyanotoxins cylindrospermopsin and 7-epi-cylindrospermopsin is catalysed by CyrI, a 2-oxoglutarate-dependent iron oxygenase. ChemBioChem 12 (2011) 858–862.
2.  Mazmouz, R., Essadik, I., Hamdane, D., Mejean, A. and Ploux, O. Characterization of CyrI, the hydroxylase involved in the last step of cylindrospermopsin biosynthesis: Binding studies, site-directed mutagenesis and stereoselectivity. Arch. Biochem. Biophys. 647 (2018) 1–9. [PMID: 29653078]
[EC 1.14.11.70 created 2019]
 
 
EC 1.14.11.71     
Accepted name: methylphosphonate hydroxylase
Reaction: methylphosphonate + 2-oxoglutarate + O2 = hydroxymethylphosphonate + succinate + CO2
Other name(s): phnY* (gene name)
Systematic name: methylphosphonate,2-oxoglutarate:oxygen oxidoreductase (1-hydroxylating)
Comments: Requires iron(II). The enzyme, characterized from the marine bacterium Gimesia maris, participates in a methylphosphonate degradation pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Gama, S.R., Vogt, M., Kalina, T., Hupp, K., Hammerschmidt, F., Pallitsch, K. and Zechel, D.L. An oxidative pathway for microbial utilization of methylphosphonic acid as a phosphate source. ACS Chem. Biol. 14 (2019) 735–741. [PMID: 30810303]
[EC 1.14.11.71 created 2019]
 
 
EC 1.14.11.72     
Accepted name: [2-(trimethylamino)ethyl]phosphonate dioxygenase
Reaction: [2-(trimethylamino)ethyl]phosphonate + 2-oxoglutarate + O2 = [(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate + succinate + CO2
Other name(s): tmpA (gene name)
Systematic name: [2-(trimethylamino)ethyl]phosphonate,2-oxoglutarate:oxygen oxidoreductase (1R-hydroxylating)
Comments: Requires Fe2+ and ascorbate. The enzyme, found in bacteria, participates in a degradation pathway for [2-(trimethylamino)ethyl]phosphonate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Rajakovich, L.J., Pandelia, M.E., Mitchell, A.J., Chang, W.C., Zhang, B., Boal, A.K., Krebs, C. and Bollinger, J.M., Jr. A new microbial pathway for organophosphonate degradation catalyzed by two previously misannotated non-heme-iron oxygenases. Biochemistry 58 (2019) 1627–1647. [PMID: 30789718]
[EC 1.14.11.72 created 2020]
 
 
EC 1.14.11.73     
Accepted name: [protein]-arginine 3-hydroxylase
Reaction: [protein]-L-arginine + 2-oxoglutarate + O2 = [protein]-(3R)-3-hydroxy-L-arginine + succinate + CO2
Other name(s): JMJD5 (gene name)
Systematic name: [protein]-L-arginine,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)
Comments: The enzyme, characterized from humans, catalyses the stereoselective formation of the (2S,3R)-hydroxy-L-arginine stereoisomer. So far the enzyme has been shown to act on two substrates - the 40S ribosomal protein S6 (RPS6), which is hydroxylated at R137, and, at a lower activity, RCCD1, a protein involved in chromatin stability, which is hydroxylated at R141. Even though the same stereoisomer is produced by the bacterial EC 1.14.11.47, [50S ribosomal protein L16]-arginine 3-hydroxylase, the two enzymes do not exhibit any cross-reactivity on their respective ribosomal protein substrates.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Wilkins, S.E., Islam, M.S., Gannon, J.M., Markolovic, S., Hopkinson, R.J., Ge, W., Schofield, C.J. and Chowdhury, R. JMJD5 is a human arginyl C-3 hydroxylase. Nat. Commun. 9:1180 (2018). [PMID: 29563586]
[EC 1.14.11.73 created 2020]
 
 
EC 1.14.11.74     
Accepted name: L-isoleucine 31-dioxygenase
Reaction: L-isoleucine + 2-oxoglutarate + O2 = 31-hydroxy-L-isoleucine + succinate + CO2
Other name(s): hilA (gene name); L-isoleucine 4′-dioxygenase (incorrect)
Systematic name: L-isoleucine,2-oxoglutarate:oxygen oxidoreductase (31-hydroxylating)
Comments: Requires Fe2+ and ascorbate. The enzyme has been characterized from the bacterium Pantoea ananatis.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Smirnov, S.V., Sokolov, P.M., Kotlyarova, V.A., Samsonova, N.N., Kodera, T., Sugiyama, M., Torii, T., Hibi, M., Shimizu, S., Yokozeki, K. and Ogawa, J. A novel L-isoleucine-4′-dioxygenase and L-isoleucine dihydroxylation cascade in Pantoea ananatis. MicrobiologyOpen 2 (2013) 471–481. [PMID: 23554367]
[EC 1.14.11.74 created 2020]
 
 
EC 1.14.11.75     
Accepted name: 31-hydroxy-L-isoleucine 4-dioxygenase
Reaction: 31-hydroxy-L-isoleucine + 2-oxoglutarate + O2 = (4S)-31,4-dihydroxy-L-isoleucine + succinate + CO2
Other name(s): hilB (gene name); 4′-hydroxy-L-isoleucine 4-dioxygenase (incorrect)
Systematic name: 31-hydroxy-L-isoleucine,2-oxoglutarate:oxygen oxidoreductase (4S-hydroxylating)
Comments: Requires Fe2+ and ascorbate. The enzyme has been characterized from the bacterium Pantoea ananatis.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Smirnov, S.V., Sokolov, P.M., Kotlyarova, V.A., Samsonova, N.N., Kodera, T., Sugiyama, M., Torii, T., Hibi, M., Shimizu, S., Yokozeki, K. and Ogawa, J. A novel L-isoleucine-4′-dioxygenase and L-isoleucine dihydroxylation cascade in Pantoea ananatis. MicrobiologyOpen 2 (2013) 471–481. [PMID: 23554367]
[EC 1.14.11.75 created 2020]
 
 
EC 1.14.11.76     
Accepted name: L-glutamate 3(R)-hydroxylase
Reaction: L-glutamate + 2-oxoglutarate + O2 = (3R)-3-hydroxy-L-glutamate + succinate + CO2
Glossary: ibotenate = (S)-2-amino-2-(3-hydroxyisoxazol-5-yl)acetate
muscimol = 5-(aminomethyl)-1,2-oxazol-3-ol
Other name(s): iboH (gene name)
Systematic name: L-glutamate,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating)
Comments: Requires Fe2+ and L-ascorbate. The enzyme, characterized from the basidiomycete mushroom Amanita muscaria, participates in the biosynthesis of the psychoactive compounds ibotenate and muscimol.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Obermaier, S. and Muller, M. Ibotenic acid biosynthesis in the fly agaric is initiated by glutamate hydroxylation. Angew. Chem. Int. Ed. Engl. 59 (2020) 12432–12435. [DOI] [PMID: 32233056]
[EC 1.14.11.76 created 2020]
 
 
EC 1.14.11.77     
Accepted name: alkyl sulfatase
Reaction: a primary alkyl sulfate ester + 2-oxoglutarate + O2 = an aldehyde + succinate + CO2 + sulfate
Other name(s): atsK (gene name); α-ketoglutarate-dependent sulfate ester dioxygenase; 2-oxoglutarate-dependent sulfate ester dioxygenase; type II alkyl sulfatase
Systematic name: primary alkyl sulfate ester, 2-oxoglutarate:oxygen oxidoreductase (sulfate-hydrolyzing)
Comments: Sulfatase enzymes are classified as type I, in which the key catalytic residue is 3-oxo-L-alanine, type II, which are non-heme iron-dependent dioxygenases, or type III, whose catalytic domain adopts a metallo-β-lactamase fold and binds two zinc ions as cofactors. The type II sulfatases oxidize the C-H bond of the carbon next to the sulfate ester, using 2-oxoglutarate and oxygen as substrates. The resulting hemiacetal sulfate ester collapses, liberating inorganic sulfate and an alkyl aldehyde along with carbon dioxide and succinate. The enzymes often desulfate a broad spectrum of linear and branched-chain sulfate esters. The enzyme from Pseudomonas putida acts on a range of medium-chain alkyl sulfate esters, with chain lengths ranging from C4 to C12. cf. sulfatase EC 3.1.6.1, arylsulfatase (type I), EC 3.1.6.21, linear primary-alkylsulfatase, and EC 3.1.6.22, branched primary-alkylsulfatase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Kahnert, A. and Kertesz, M.A. Characterization of a sulfur-regulated oxygenative alkylsulfatase from Pseudomonas putida S-313. J. Biol. Chem. 275 (2000) 31661–31667. [DOI] [PMID: 10913158]
2.  Muller, I., Kahnert, A., Pape, T., Sheldrick, G.M., Meyer-Klaucke, W., Dierks, T., Kertesz, M. and Uson, I. Crystal structure of the alkylsulfatase AtsK: insights into the catalytic mechanism of the Fe(II) α-ketoglutarate-dependent dioxygenase superfamily. Biochemistry 43 (2004) 3075–3088. [DOI] [PMID: 15023059]
3.  Sogi, K.M., Gartner, Z.J., Breidenbach, M.A., Appel, M.J., Schelle, M.W. and Bertozzi, C.R. Mycobacterium tuberculosis Rv3406 is a type II alkyl sulfatase capable of sulfate scavenging. PLoS One 8:e65080 (2013). [DOI] [PMID: 23762287]
[EC 1.14.11.77 created 2021]
 
 
EC 1.14.11.78     
Accepted name: (R)-3-[(carboxymethyl)amino]fatty acid dioxygenase/decarboxylase
Reaction: a (3R)-3-[(carboxylmethyl)amino]fatty acid + 2 2-oxoglutarate + 2 O2 = a (3R)-3-isocyanyl-fatty acid + 2 succinate + 3 CO2 + 2 H2O (overall reaction)
(1a) a (3R)-3-[(carboxylmethyl)amino]fatty acid + 2-oxoglutarate + O2 = a (3R)-3-{[carboxy(hydroxy)methyl]amino}fatty acid + succinate + CO2
(1b) a (3R)-3-{[carboxy(hydroxy)methyl]amino}fatty acid + 2-oxoglutarate + O2 = a (3R)-3-isocyanyl-fatty acid + succinate + 2 CO2 + 2 H2O
Other name(s): scoE (gene name); mmaE (gene name); Rv0097 (locus name)
Systematic name: (3R)-3-[(carboxylmethyl)amino]fatty acid,2-oxoglutarate:oxygen oxidoreductase (isonitrile-forming)
Comments: Requires Fe(II). The enzyme, found in actinobacterial species, participates in the biosynthesis of isonitrile-containing lipopeptides. The reaction comprises two catalytic cycles, each consuming an oxygen molecule and a 2-oxoglutarate molecule. In the first cycle the substrate is hydroxylated, while in the second cycle the enzyme catalyses a decarboxylation/oxidation reaction that produces an isonitrile group.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Harris, N.C., Sato, M., Herman, N.A., Twigg, F., Cai, W., Liu, J., Zhu, X., Downey, J., Khalaf, R., Martin, J., Koshino, H. and Zhang, W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc. Natl. Acad. Sci. USA 114 (2017) 7025–7030. [DOI] [PMID: 28634299]
2.  Harris, N.C., Born, D.A., Cai, W., Huang, Y., Martin, J., Khalaf, R., Drennan, C.L. and Zhang, W. Isonitrile formation by a non-heme iron(II)-dependent oxidase/decarboxylase. Angew. Chem. Int. Ed. Engl. 57 (2018) 9707–9710. [DOI] [PMID: 29906336]
3.  Jonnalagadda, R., Del Rio Flores, A., Cai, W., Mehmood, R., Narayanamoorthy, M., Ren, C., Zaragoza, J.PT., Kulik, H.J., Zhang, W. and Drennan, C.L. Biochemical and crystallographic investigations into isonitrile formation by a nonheme iron-dependent oxidase/decarboxylase. J. Biol. Chem. 296:100231 (2021). [DOI] [PMID: 33361191]
[EC 1.14.11.78 created 2022]
 
 
EC 1.14.11.79     
Accepted name: protein-L-histidine (3S)-3-hydroxylase
Reaction: a [protein]-L-histidine + 2-oxoglutarate + O2 = a [protein]-(3S)-3-hydroxy-L-histidine + succinate + CO2
Other name(s): RIOX1 (gene name); RIOX2 (gene name); protein histidyl hydroxylase
Systematic name: protein-L-histidine,2-oxoglutarate:oxygen oxidoreductase (3S-hydroxylating)
Comments: The human enzymes encoded by the RIOX1 and RIOX2 genes catalyse the hydroxylation of L-histidine residues in the 60S ribosomal proteins Rpl8 and L27a, respectively. Both proteins contain JmjC and winged helix domains, and both also catalyse histone L-lysine demethylation activities.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Ge, W., Wolf, A., Feng, T., Ho, C.H., Sekirnik, R., Zayer, A., Granatino, N., Cockman, M.E., Loenarz, C., Loik, N.D., Hardy, A.P., Claridge, T.DW., Hamed, R.B., Chowdhury, R., Gong, L., Robinson, C.V., Trudgian, D.C., Jiang, M., Mackeen, M.M., Mccullagh, J.S., Gordiyenko, Y., Thalhammer, A., Yamamoto, A., Yang, M., Liu-Yi, P., Zhang, Z., Schmidt-Zachmann, M., Kessler, B.M., Ratcliffe, P.J., Preston, G.M., Coleman, M.L. and Schofield, C.J. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans. Nat. Chem. Biol. 8 (2012) 960–962. [DOI] [PMID: 23103944]
2.  Bundred, J.R., Hendrix, E. and Coleman, M.L. The emerging roles of ribosomal histidyl hydroxylases in cell biology, physiology and disease. Cell. Mol. Life Sci. 75 (2018) 4093–4105. [DOI] [PMID: 30151692]
[EC 1.14.11.79 created 2022]
 
 
EC 1.14.11.80     
Accepted name: methylcytosine dioxygenase
Reaction: (1) 5-methylcytosine in DNA + 2-oxoglutarate + O2 = 5-hydroxymethylcytosine in DNA + succinate + CO2
(2) 5-hydroxymethylcytosine in DNA + 2-oxoglutarate + O2 = 5-formylcytosine in DNA + succinate + CO2 + H2O
(3) 5-formylcytosine in DNA + 2-oxoglutarate + O2 = 5-carboxycytosine in DNA + succinate + CO2
Other name(s): TET1 (gene name); TET2 (gene name); TET3 (gene name)
Systematic name: 5-methylcytosine in DNA,2-oxoglutarate:oxygen oxidoreductase
Comments: The TET proteins mediate iterative oxidation of 5-methylcytosine in DNA (5mc) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are recognized by EC 3.2.2.29, thymine-DNA glycosylase (TDG), which excises them, leaving an apyrimidinic site. Coupled with the base excision repair (BER) pathway, these activities result in a cytosine demethylation pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C. and Zhang, Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466 (2010) 1129–1133. [DOI] [PMID: 20639862]
2.  Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C. and Zhang, Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333 (2011) 1300–1303. [DOI] [PMID: 21778364]
3.  He, Y.F., Li, B.Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.X., Zhang, K., He, C. and Xu, G.L. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333 (2011) 1303–1307. [DOI] [PMID: 21817016]
4.  Maiti, A. and Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J. Biol. Chem. 286 (2011) 35334–35338. [DOI] [PMID: 21862836]
5.  Zhang, L., Lu, X., Lu, J., Liang, H., Dai, Q., Xu, G.L., Luo, C., Jiang, H. and He, C. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol. 8 (2012) 328–330. [DOI] [PMID: 22327402]
[EC 1.14.11.80 created 2022]
 
 
EC 1.14.11.81     
Accepted name: (–)-cyclopenine synthase
Reaction: (1) cyclopeptine + 2-oxoglutarate + O2 = dehydrocyclopeptine + succinate + CO2 + H2O
(2) dehydrocyclopeptine + 2-oxoglutarate + O2 = (–)-cyclopenine + succinate + CO2
For diagram of cyclopeptine, cyclopenine and viridicatin biosynthesis, click here
Glossary: cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
(–)-cyclopenine = (3S,3′R)-4-methyl-3′-phenyl-1H-spiro[1,4-benzodiazepine-3,2′-oxirane]-2,5-dione
Other name(s): asqJ (gene name)
Systematic name: cyclopeptine,2-oxoglutarate:oxygen oxidoreductase ((–)-cyclopenine-forming)
Comments: This fungal enzyme is involved in the biosynthesis of quinolone compounds. it catalyses two oxidation reactions: the first reaction results in a desaturation; the second reaction is a monooxygenation of the double bond, forming an epoxide. The enzyme is also active with 4′-methoxycyclopeptine.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Nover, L. and Luckner, M. Mixed functional oxygenations during the biosynthesis of cyclopenin and cyclopenol, benzodiazepine alkaloids of Penicillium cyclopium westling. Incorporation of molecular oxygen and NIH-shift. FEBS Lett. 3 (1969) 292–296. [DOI] [PMID: 11947032]
2.  Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880–12884. [DOI] [PMID: 25251934]
3.  Brauer, A., Beck, P., Hintermann, L. and Groll, M. Structure of the dioxygenase AsqJ: Mechanistic insights into a one-pot multistep quinolone antibiotic biosynthesis. Angew. Chem. Int. Ed. Engl. 55 (2016) 422–426. [DOI] [PMID: 26553478]
4.  Chang, W.C., Li, J., Lee, J.L., Cronican, A.A. and Guo, Y. Mechanistic investigation of a non-heme iron enzyme catalyzed epoxidation in (–)-4′-methoxycyclopenin biosynthesis. J. Am. Chem. Soc. 138 (2016) 10390–10393. [DOI] [PMID: 27442345]
5.  Song, X., Lu, J. and Lai, W. Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations. Phys Chem Chem Phys 19 (2017) 20188–20197. [DOI] [PMID: 28726913]
6.  Liao, H.J., Li, J., Huang, J.L., Davidson, M., Kurnikov, I., Lin, T.S., Lee, J.L., Kurnikova, M., Guo, Y., Chan, N.L. and Chang, W.C. Insights into the desaturation of cyclopeptin and its C3 epimer catalyzed by a non-heme iron enzyme: structural characterization and mechanism elucidation. Angew. Chem. Int. Ed. Engl. 57 (2018) 1831–1835. [DOI] [PMID: 29314482]
7.  Mader, S.L., Brauer, A., Groll, M. and Kaila, V.RI. Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ. Nat. Commun. 9:1168 (2018). [DOI] [PMID: 29563492]
8.  Wojdyla, Z. and Borowski, T. On how the binding cavity of AsqJ dioxygenase controls the desaturation reaction regioselectivity: a QM/MM study. J. Biol. Inorg. Chem. 23 (2018) 795–808. [DOI] [PMID: 29876666]
9.  Li, J., Liao, H.J., Tang, Y., Huang, J.L., Cha, L., Lin, T.S., Lee, J.L., Kurnikov, I.V., Kurnikova, M.G., Chang, W.C., Chan, N.L. and Guo, Y. Epoxidation catalyzed by the nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase, AsqJ: mechanistic elucidation of oxygen atom transfer by a ferryl intermediate. J. Am. Chem. Soc. 142 (2020) 6268–6284. [DOI] [PMID: 32131594]
10.  Tang, H., Tang, Y., Kurnikov, I.V., Liao, H.J., Chan, N.L., Kurnikova, M.G., Guo, Y. and Chang, W.C. Harnessing the substrate promiscuity of dioxygenase AsqJ and developing efficient chemoenzymatic synthesis for quinolones. ACS Catal. 11 (2021) 7186–7192. [DOI] [PMID: 35721870]
[EC 1.14.11.81 created 2022]
 
 
EC 1.14.11.82     
Accepted name: 5-dehydro-6-demethoxyfumagillol dioxygenase
Reaction: 5-dehydro-6-demethoxyfumagillol + 2-oxoglutarate + O2 = 5-dehydro-6-demethoxy-6-hydroxyfumagillol + succinate + CO2
For diagram of santalene and bergamotene biosynthesis, click here
Glossary: fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
Other name(s): fmaF (gene name); Fma-C6H
Systematic name: 5-dehydro-6-demethoxyfumagillol,2-oxoglutarate:oxygen oxidoreductase (6-hydroxylating)
Comments: Requires iron(II). The enzyme, characterized from the mold Aspergillus fumigatus, participates in the biosynthesis of the meroterpenoid fumagillin.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426–4436. [DOI] [PMID: 24568283]
[EC 1.14.11.82 created 2022]
 
 
EC 1.14.20.1     
Accepted name: deacetoxycephalosporin-C synthase
Reaction: penicillin N + 2-oxoglutarate + O2 = deacetoxycephalosporin C + succinate + CO2 + H2O
For diagram of penicillin-N and deacetoxycephalosporin-C biosynthesis, click here
Other name(s): DAOCS; penicillin N expandase; DAOC synthase
Systematic name: penicillin-N,2-oxoglutarate:oxygen oxidoreductase (ring-expanding)
Comments: Forms part of the penicillin biosynthesis pathway (for pathway, click here).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 85746-10-7
References:
1.  Cantwell, C., Beckmann, R., Whiteman, P., Queener, S.W. and Abraham, E.P. Isolation of deacetoxycephalosporin-c from fermentation broths of Penicillium chrysogenum transformants - construction of a new fungal biosynthetic-pathway. Proc. R. Soc. Lond. B Biol. Sci. 248 (1992) 283–289. [DOI] [PMID: 1354366]
2.  Lee, H.J., Lloyd, M.D., Harlos, K., Clifton, I.J., Baldwin, J.E. and Schofield, C.J. Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS). J. Mol. Biol. 308 (2001) 937–948. [DOI] [PMID: 11352583]
3.  Yeh, W.K., Ghag, S.K. and Queener, S.W. Enzymes for epimerization of isopenicillin N, ring expansion of penicillin N, and 3′-hydroxylation of deacetoxycephalosporin C. Function, evolution, refolding, and enzyme engineering. Ann. N.Y. Acad. Sci. 672 (1992) 396–408.
4.  Valegaard, K., van Scheltinga, A.C.T., Lloyd, M.D., Hara, T., Ramaswamy, S., Perrakis, A., Thompson, A., Lee, H.-J., Baldwin, J.E., Schofield, C.J., Hajdu, J. and Andersson, I. Structure of a cephalosporin synthase. Nature 394 (1998) 805–809. [DOI] [PMID: 9723623]
5.  Dotzlaf, J.E. and Yeh, W.K. Purification and properties of deacetoxycephalosporin C synthase from recombinant Escherichia coli and its comparison with the native enzyme purified from Streptomyces clavuligerus. J. Biol. Chem. 264 (1989) 10219–10227. [PMID: 2656705]
[EC 1.14.20.1 created 2002]
 
 
EC 1.14.20.2      
Transferred entry: 2,4-dihydroxy-1,4-benzoxazin-3-one-glucoside dioxygenase. Now EC 1.14.11.59, 2,4-dihydroxy-1,4-benzoxazin-3-one-glucoside dioxygenase
[EC 1.14.20.2 created 2012, deleted 2018]
 
 
EC 1.14.20.3     
Accepted name: (5R)-carbapenem-3-carboxylate synthase
Reaction: (3S,5S)-carbapenam-3-carboxylate + 2-oxoglutarate + O2 = (5R)-carbapen-2-em-3-carboxylate + succinate + CO2 + H2O
Glossary: (3S,5S)-carbapenam-3-carboxylate = (2S,5S)-7-oxo-1-azabicyclo[3.2.0]heptane-2-carboxylate
(5R)-carbapen-2-em-3-carboxylate = (5R)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
Other name(s): carC (gene name)
Systematic name: (3S,5S)-carbapenam-3-carboxylate,2-oxoglutarate:oxygen oxidoreductase (dehydrating)
Comments: Requires Fe2+. The enzyme is involved in the biosynthesis of the carbapenem β-lactam antibiotic (5R)-carbapen-2-em-3-carboxylate in the bacterium Pectobacterium carotovorum. It catalyses a stereoinversion at C-5 and introduces a double bond between C-2 and C-3.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Clifton, I.J., Doan, L.X., Sleeman, M.C., Topf, M., Suzuki, H., Wilmouth, R.C. and Schofield, C.J. Crystal structure of carbapenem synthase (CarC). J. Biol. Chem. 278 (2003) 20843–20850. [DOI] [PMID: 12611886]
2.  Stapon, A., Li, R. and Townsend, C.A. Carbapenem biosynthesis: confirmation of stereochemical assignments and the role of CarC in the ring stereoinversion process from L-proline. J. Am. Chem. Soc. 125 (2003) 8486–8493. [DOI] [PMID: 12848554]
3.  Sleeman, M.C., Smith, P., Kellam, B., Chhabra, S.R., Bycroft, B.W. and Schofield, C.J. Biosynthesis of carbapenem antibiotics: new carbapenam substrates for carbapenem synthase (CarC). ChemBioChem 5 (2004) 879–882. [DOI] [PMID: 15174175]
[EC 1.14.20.3 created 2013]
 
 
EC 1.14.20.4     
Accepted name: anthocyanidin synthase
Reaction: a (2R,3S,4S)-leucoanthocyanidin + 2-oxoglutarate + O2 = an anthocyanidin + succinate + CO2 + 2 H2O (overall reaction)
(1a) a (2R,3S,4S)-leucoanthocyanidin + 2-oxoglutarate + O2 = a (4S)- 2,3-dehydroflavan-3,4-diol + succinate + CO2 + H2O
(1b) a (4S)- 2,3-dehydroflavan-3,4-diol = an anthocyanidin + H2O
For diagram of anthocyanin biosynthesis, click here
Glossary: taxifolin = 3,4-dihydroquercitin
Other name(s): leucocyanidin oxygenase; leucocyanidin,2-oxoglutarate:oxygen oxidoreductase; ANS (gene name)
Systematic name: (2R,3S,4S)-leucoanthocyanidin,2-oxoglutarate:oxygen oxidoreductase
Comments: The enzyme requires iron(II) and ascorbate. It is involved in the pathway by which many flowering plants make anthocyanin flower pigments (glycosylated anthocyandins). The enzyme hydroxylates the C-3 carbon, followed by a trans diaxial elimination, forming a C-2,C-3 enol. The product loses a second water molecule to form anthocyanidins. When assayed in vitro, non-enzymic epimerization of the product can lead to formation of dihydroflavanols. Thus when the substrate is leucocyanidin, a mixture of (+)-taxifolin and (+)-epitaxifolin are formed. The enzyme can also oxidize the formed (+)-taxifolin to quercetin (cf. EC 1.14.20.6, flavonol synthase) [2,3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 180984-01-4
References:
1.  Saito, K., Kobayashi, M., Gong, Z., Tanaka, Y. and Yamazaki, M. Direct evidence for anthocyanidin synthase as a 2-oxoglutarate-dependent oxygenase: molecular cloning and functional expression of cDNA from a red forma of Perilla frutescens. Plant J. 17 (1999) 181–190. [DOI] [PMID: 10074715]
2.  Turnbull, J.J., Sobey, W.J., Aplin, R.T., Hassan, A., Firmin, J.L., Schofield, C.J. and Prescott, A.G. Are anthocyanidins the immediate products of anthocyanidin synthase? Chem. Commun. (2000) 2473–2474.
3.  Wilmouth, R.C., Turnbull, J.J., Welford, R.W., Clifton, I.J., Prescott, A.G. and Schofield, C.J. Structure and mechanism of anthocyanidin synthase from Arabidopsis thaliana. Structure 10 (2002) 93–103. [DOI] [PMID: 11796114]
4.  Turnbull, J.J., Nagle, M.J., Seibel, J.F., Welford, R.W., Grant, G.H. and Schofield, C.J. The C-4 stereochemistry of leucocyanidin substrates for anthocyanidin synthase affects product selectivity. Bioorg. Med. Chem. Lett. 13 (2003) 3853–3857. [DOI] [PMID: 14552794]
5.  Wellmann, F., Griesser, M., Schwab, W., Martens, S., Eisenreich, W., Matern, U. and Lukacin, R. Anthocyanidin synthase from Gerbera hybrida catalyzes the conversion of (+)-catechin to cyanidin and a novel procyanidin. FEBS Lett. 580 (2006) 1642–1648. [DOI] [PMID: 16494872]
[EC 1.14.20.4 created 2001 as EC 1.14.11.19, transferred 2018 to EC 1.14.20.4]
 
 
EC 1.14.20.5     
Accepted name: flavone synthase I
Reaction: a flavanone + 2-oxoglutarate + O2 = a flavone + succinate + CO2 + H2O
For diagram of flavonoid biosynthesis, click here and for diagram of the biosynthesis of naringenin derivatives, click here
Other name(s): FNSI (gene name)
Systematic name: flavanone,2-oxoglutarate:oxygen oxidoreductase (dehydrating)
Comments: The enzyme, which has been found in rice and in members of the Apiaceae (a plant family), is a member of the 2-oxoglutarate-dependent dioxygenases, and requires ascorbate and Fe2+ for full activity.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 138263-98-6
References:
1.  Martens, S., Forkmann, G., Matern, U. and Lukačin, R. Cloning of parsley flavone synthase I. Phytochemistry 58 (2001) 43–46. [DOI] [PMID: 11524111]
2.  Lukačin, R., Matern, U., Junghanns, K.T., Heskamp, M.L., Britsch, L., Forkmann, G. and Martens, S. Purification and antigenicity of flavone synthase I from irradiated parsley cells. Arch. Biochem. Biophys. 393 (2001) 177–183. [DOI] [PMID: 11516175]
3.  Martens, S., Forkmann, G., Britsch, L., Wellmann, F., Matern, U. and Lukačin, R. Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley. FEBS Lett. 544 (2003) 93–98. [DOI] [PMID: 12782296]
[EC 1.14.20.5 created 2004 as EC 1.14.11.22, transferred 2018 to EC 1.14.20.5]
 
 
EC 1.14.20.6     
Accepted name: flavonol synthase
Reaction: a dihydroflavonol + 2-oxoglutarate + O2 = a flavonol + succinate + CO2 + H2O
For diagram of flavonoid biosynthesis, click here, for diagram of kaempferol biosynthesis, click here and for diagram of myricetin biosynthesis, click here
Other name(s): FLS (gene name)
Systematic name: dihydroflavonol,2-oxoglutarate:oxygen oxidoreductase
Comments: In addition to the desaturation of (2R,3R)-dihydroflavonols to flavonols, the enzyme from Citrus unshiu (satsuma mandarin) also has a non-specific activity that trans-hydroxylates the flavanones (2S)-naringenin and the unnatural (2R)-naringenin at C-3 to kaempferol and (2R,3R)-dihydrokaempferol, respectively [2]. Requires Fe2+.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 146359-76-4
References:
1.  Wellmann, F., Lukačin, R., Moriguchi, T., Britsch, L., Schiltz, E. and Matern, U. Functional expression and mutational analysis of flavonol synthase from Citrus unshiu. Eur. J. Biochem. 269 (2002) 4134–4142. [DOI] [PMID: 12180990]
2.  Lukačin, R., Wellmann, F., Britsch, L., Martens, S. and Matern, U. Flavonol synthase from Citrus unshiu is a bifunctional dioxygenase. Phytochemistry 62 (2003) 287–292. [DOI] [PMID: 12620339]
3.  Martens, S., Forkmann, G., Britsch, L., Wellmann, F., Matern, U. and Lukačin, R. Divergent evolution of flavonoid 2-oxoglutarate-dependent dioxygenases in parsley. FEBS Lett. 544 (2003) 93–98. [DOI] [PMID: 12782296]
4.  Turnbull, J.J., Nakajima, J., Welford, R.W., Yamazaki, M., Saito, K. and Schofield, C.J. Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis: anthocyanidin synthase, flavonol synthase, and flavanone 3β-hydroxylase. J. Biol. Chem. 279 (2004) 1206–1216. [DOI] [PMID: 14570878]
[EC 1.14.20.6 created 2004 as EC 1.14.11.23, transferred 2018 to EC 1.14.20.6]
 
 
EC 1.14.20.7     
Accepted name: 2-oxoglutarate/L-arginine monooxygenase/decarboxylase (succinate-forming)
Reaction: L-arginine + 2-oxoglutarate + O2 = L-glutamate 5-semialdehyde + guanidine + succinate + CO2 (overall reaction)
(1a) L-arginine + 2-oxoglutarate + O2 = 5-hydroxy-L-arginine + succinate + CO2
(1b) 5-hydroxy-L-arginine = L-glutamate 5-semialdehyde + guanidine
Other name(s): ethene-forming enzyme; ethylene-forming enzyme; EFE
Systematic name: L-arginine,2-oxoglutarate:oxygen oxidoreductase (succinate-forming)
Comments: This is one of two simultaneous reactions catalysed by the enzyme, which is responsible for ethene (ethylene) production in bacteria of the Pseudomonas syringae group. In the other reaction [EC 1.13.12.19, 2-oxoglutarate dioxygenase (ethene-forming)] the enzyme catalyses the dioxygenation of 2-oxoglutarate forming ethene and three molecules of carbon dioxide.The enzyme catalyses two cycles of the ethene-forming reaction for each cycle of the succinate-forming reaction, so that the stoichiometry of the products ethene and succinate is 2:1. The product of the enzyme, L-glutamate 5-semialdehyde, exists in equilibrium with the cyclic form (S)-1-pyrroline-5-carboxylate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Nagahama, K., Ogawa, T., Fujii, T., Tazaki, M., Tanase, S., Morino, Y. and Fukuda, H. Purification and properties of an ethylene-forming enzyme from Pseudomonas syringae pv. phaseolicola PK2. J. Gen. Microbiol. 137 (1991) 2281–2286. [DOI] [PMID: 1770346]
2.  Fukuda, H., Ogawa, T., Tazaki, M., Nagahama, K., Fujii, T., Tanase, S. and Morino, Y. Two reactions are simultaneously catalyzed by a single enzyme: the arginine-dependent simultaneous formation of two products, ethylene and succinate, from 2-oxoglutarate by an enzyme from Pseudomonas syringae. Biochem. Biophys. Res. Commun. 188 (1992) 483–489. [DOI] [PMID: 1445291]
3.  Fukuda, H., Ogawa, T., Ishihara, K., Fujii, T., Nagahama, K., Omata, T., Inoue, Y., Tanase, S. and Morino, Y. Molecular cloning in Escherichia coli, expression, and nucleotide sequence of the gene for the ethylene-forming enzyme of Pseudomonas syringae pv. phaseolicola PK2. Biochem. Biophys. Res. Commun. 188 (1992) 826–832. [DOI] [PMID: 1445325]
4.  Martinez, S., Fellner, M., Herr, C.Q., Ritchie, A., Hu, J. and Hausinger, R.P. Structures and mechanisms of the non-heme Fe(II)- and 2-oxoglutarate-dependent ethylene-forming enzyme: substrate binding creates a twist. J. Am. Chem. Soc. 139 (2017) 11980–11988. [DOI] [PMID: 28780854]
[EC 1.14.20.7 created 2011 as EC 1.14.11.34, transferred 2018 to EC 1.14.20.7, modified 2023]
 
 
EC 1.14.20.8     
Accepted name: (–)-deoxypodophyllotoxin synthase
Reaction: (–)-yatein + 2-oxoglutarate + O2 = (–)-deoxypodophyllotoxin + succinate + CO2 + H2O
For diagram of podophyllotoxin biosynthesis, click here
Glossary: (–)-yatein = (3R,4R)-4-(1,3-benzodioxol-5-ylmethyl)-3-(3,4,5-trimethoxybenzyl)dihydrofuran-2(3H)-one
(–)-deoxypodophyllotoxin = (5R,5aR,8aR)-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-6(5a)-one
Other name(s): 2-ODD (gene name)
Systematic name: (–)-yatein,2-oxoglutarate:oxygen oxidoreductase (ring-forming)
Comments: The enzyme, characterized from the plant Sinopodophyllum hexandrum (mayapple), is involved in the biosynthetic pathway of podophyllotoxin, a non-alkaloid toxin lignan whose derivatives are important anticancer drugs. It catalyses the closure of the central six-membered ring in the aryltetralin scaffold.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
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 1.14.20.8 created 2016 as EC 1.14.11.50, transferred 2018 to EC 1.14.20.8]
 
 
EC 1.14.20.9     
Accepted name: L-tyrosine isonitrile desaturase
Reaction: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = (2E)-3-(4-hydroxyphenyl)-2-isocyanoprop-2-enoate + succinate + CO2 + H2O
Glossary: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoic acid = L-tyrosine isonitrile
paerucumarin = 6,7-dihydroxy-3-isocyanochromen-2-one
Other name(s): pvcB (gene name)
Systematic name: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase
Comments: The enzyme is a member of the Fe2+, 2-oxoglutarate-dependent oxygenases and requires Fe2+. It has been characterized from bacteria that form the isonitrile-functionalized compound paerucumarin. cf. EC 1.14.20.10, L-tyrosine isonitrile desaturase/decarboxylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Clarke-Pearson, M.F. and Brady, S.F. Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J. Bacteriol. 190 (2008) 6927–6930. [DOI] [PMID: 18689486]
2.  Drake, E.J. and Gulick, A.M. Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J. Mol. Biol. 384 (2008) 193–205. [DOI] [PMID: 18824174]
3.  Zhu, J., Lippa, G.M., Gulick, A.M. and Tipton, P.A. Examining reaction specificity in PvcB, a source of diversity in isonitrile-containing natural products. Biochemistry 54 (2015) 2659–2669. [DOI] [PMID: 25866990]
[EC 1.14.20.9 created 2018]
 
 
EC 1.14.20.10     
Accepted name: L-tyrosine isonitrile desaturase/decarboxylase
Reaction: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = 4-[(E)-2-isocyanoethenyl]phenol + succinate + 2 CO2 + H2O
Glossary: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoic acid = L-tyrosine isonitrile
rhabduscin = N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-{4-[(E)-2-isocyanoethenyl]phenoxy}-2-methyloxan-3-yl]acetamide
Other name(s): pvcB (gene name)
Systematic name: (2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating)
Comments: The enzyme, characterized from the bacterium Xenorhabdus nematophila, is involved in rhabduscin biosynthesis. The enzyme is a member of the Fe2+, 2-oxoglutarate-dependent oxygenases. It is similar to EC 1.14.20.9, L-tyrosine isonitrile desaturase. However, the latter does not catalyse a decarboxylation of the substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Crawford, J.M., Portmann, C., Zhang, X., Roeffaers, M.B. and Clardy, J. Small molecule perimeter defense in entomopathogenic bacteria. Proc. Natl. Acad. Sci. USA 109 (2012) 10821–10826. [DOI] [PMID: 22711807]
2.  Zhu, J., Lippa, G.M., Gulick, A.M. and Tipton, P.A. Examining reaction specificity in PvcB, a source of diversity in isonitrile-containing natural products. Biochemistry 54 (2015) 2659–2669. [DOI] [PMID: 25866990]
[EC 1.14.20.10 created 2018]
 
 
EC 1.14.20.11     
Accepted name: 3-[(Z)-2-isocyanoethenyl]-1H-indole synthase
Reaction: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = 3-[(Z)-2-isocyanoethenyl]-1H-indole + succinate + 2 CO2 + H2O
For diagram of tryptophan isonitrile biosynthesis, click here
Glossary: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile
Other name(s): ambI3 (gene name); famH3 (gene name); L-tryptophan isonitrile desaturase/decarboxylase (3-[(Z)-2-isocyanoethenyl]-1H-indole-forming)
Systematic name: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating, 3-[(Z)-2-isocyanoethenyl]-1H-indole-forming)
Comments: The enzyme, characterized from the cyanobacterium Fischerella ambigua UTEX 1903, participates in the biosynthesis of hapalindole-type alkaloids. The enzyme catalyses an Fe2+, 2-oxoglutarate-dependent monooxygenation at C-3, which is followed by decarboxylation and dehydration, resulting in the generation of a cis C-C double bond. cf. EC 1.14.20.12, 3-[(E)-2-isocyanoethenyl]-1H-indole synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Hillwig, M.L., Zhu, Q. and Liu, X. Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem. Biol. 9 (2014) 372–377. [DOI] [PMID: 24180436]
2.  Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208–1211. [DOI] [PMID: 28212039]
[EC 1.14.20.11 created 2018]
 
 
EC 1.14.20.12     
Accepted name: 3-[(E)-2-isocyanoethenyl]-1H-indole synthase
Reaction: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate + 2-oxoglutarate + O2 = 3-[(E)-2-isocyanoethenyl]-1H-indole + succinate + 2 CO2 + H2O
Glossary: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate = L-tryptophan isonitrile
Other name(s): isnB (gene name); L-tryptophan isonitrile desaturase/decarboxylase (3-[(E)-2-isocyanoethenyl]-1H-indole-forming)
Systematic name: (2S)-3-(1H-indol-3-yl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating, 3-[(E)-2-isocyanoethenyl]-1H-indole-forming)
Comments: The enzyme has been characterized from an unidentified soil bacterium. It catalyses an Fe2+, 2-oxoglutarate-dependent monooxygenation at C-3, which is followed by decarboxylation and dehydration, resulting in the generation of a trans C-C double bond. cf. EC 1.14.20.11, 3-[(Z)-2-isocyanoethenyl]-1H-indole synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Brady, S.F. and Clardy, J. Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew. Chem. Int. Ed. Engl. 44 (2005) 7063–7065. [PMID: 16206308]
2.  Chang, W.C., Sanyal, D., Huang, J.L., Ittiamornkul, K., Zhu, Q. and Liu, X. In vitro stepwise reconstitution of amino acid derived vinyl isocyanide biosynthesis: detection of an elusive intermediate. Org. Lett. 19 (2017) 1208–1211. [DOI] [PMID: 28212039]
[EC 1.14.20.12 created 2018]
 
 
EC 1.14.20.13     
Accepted name: 6β-hydroxyhyoscyamine epoxidase
Reaction: (6S)-6β-hydroxyhyoscyamine + 2-oxoglutarate + O2 = scopolamine + succinate + CO2 + H2O
For diagram of tropane alkaloid biosynthesis, click here
Glossary: scopolamine = hyoscine = (1R,2R,4S,5S,7s)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl (2S)-3-hydroxy-2-phenylpropanoate
Other name(s): hydroxyhyoscyamine dioxygenase; (6S)-6-hydroxyhyoscyamine,2-oxoglutarate oxidoreductase (epoxide-forming)
Systematic name: (6S)-6β-hydroxyhyoscyamine,2-oxoglutarate:oxygen oxidoreductase (epoxide-forming)
Comments: Requires Fe2+ and ascorbate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 121479-53-6
References:
1.  Hashimoto, T., Kohno, J. and Yamada, Y. 6β-Hydroxyhyoscyamine epoxidase from cultured roots of Hyoscyamus niger. Phytochemistry 28 (1989) 1077–1082.
[EC 1.14.20.13 created 1992 as EC 1.14.11.14, transferred 2018 to EC 1.14.20.13]
 
 
EC 1.14.20.14     
Accepted name: hapalindole-type alkaloid chlorinase
Reaction: (1) hapalindole U + 2-oxoglutarate + O2 + chloride = hapalindole G + succinate + CO2 + H2O
(2)12-epi-fischerindole U + 2-oxoglutarate + O2 + chloride = 12-epi-fischerindole G + succinate + CO2 + H2O
For diagram of hapalindole/fischerindole biosynthesis, click here
Glossary: 12-epi-fischerindole U = (6aS,9S,10R,10aS)-9-ethenyl-10-isocyano-6,6,9-trimethyl-5,6,6a,7,8,9,10,10a-octahydroindeno[2,1-b]indole
12-epi-fischerindole G = (6aR,8R,9S,10R,10aS)-8-chloro-9-ethenyl-10-isocyano-6,6,9-trimethyl-5,6,6a,7,8,9,10,10a-octahydroindeno[2,1-b]indole
Other name(s): ambO5 (gene name); welO5 (gene name)
Systematic name: 12-epi-fischerindole U,2-oxoglutarate:oxygen oxidoreductase (13-halogenating)
Comments: The enzyme, characterized from hapalindole-type alkaloids-producing cyanobacteria, is a specialized iron(II)/2-oxoglutarate-dependent oxygenase that catalyses the chlorination of its substrates in a reaction that requires oxygen, chloride ions, iron(II) and 2-oxoglutarate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Hillwig, M.L. and Liu, X. A new family of iron-dependent halogenases acts on freestanding substrates. Nat. Chem. Biol. 10 (2014) 921–923. [PMID: 25218740]
2.  Zhu, Q., Hillwig, M.L., Doi, Y. and Liu, X. Aliphatic halogenase enables late-stage C-H functionalization: selective synthesis of a brominated fischerindole alkaloid with enhanced antibacterial activity. ChemBioChem 17 (2016) 466–470. [PMID: 26749394]
3.  Hillwig, M.L., Zhu, Q., Ittiamornkul, K. and Liu, X. Discovery of a promiscuous non-heme iron halogenase in ambiguine alkaloid biogenesis: implication for an evolvable enzyme family for late-stage halogenation of aliphatic carbons in small molecules. Angew. Chem. Int. Ed. Engl. 55 (2016) 5780–5784. [PMID: 27027281]
[EC 1.14.20.14 created 2018]
 
 
EC 1.14.20.15     
Accepted name: L-threonyl-[L-threonyl-carrier protein] 4-chlorinase
Reaction: an L-threonyl-[L-threonyl-carrier protein] + 2-oxoglutarate + O2 + Cl- = a 4-chloro-L-threonyl-[L-threonyl-carrier protein] + succinate + CO2 + H2O
Other name(s): syrB2 (gene name)
Systematic name: L-threonyl-[L-threonyl-carrier protein],2-oxoglutarate:oxygen oxidoreductase (4-halogenating)
Comments: The enzyme, characterized from the bacterium Pseudomonas syringae, participates in syringomycin E biosynthesis. The enzyme is a specialized iron(II)/2-oxoglutarate-dependent oxygenase that catalyses the chlorination of its substrate in a reaction that requires oxygen, chloride ions, ferrous iron and 2-oxoglutarate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Vaillancourt, F.H., Yin, J. and Walsh, C.T. SyrB2 in syringomycin E biosynthesis is a nonheme FeII α-ketoglutarate- and O2-dependent halogenase. Proc. Natl. Acad. Sci. USA 102 (2005) 10111–10116. [DOI] [PMID: 16002467]
[EC 1.14.20.15 created 2018]
 
 
EC 1.14.99.66     
Accepted name: [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase
Reaction: a [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 acceptor + 2 H2O = a [histone H3]-L-lysine4 + 2 formaldehyde + 2 reduced acceptor (overall reaction)
(1a) a [histone H3]-N6,N6-dimethyl-L-lysine4 + acceptor + H2O = a [histone H3]-N6-methyl-L-lysine4 + formaldehyde + reduced acceptor
(1b) a [histone H3]-N6-methyl-L-lysine4 + acceptor + H2O = a [histone H3]-L-lysine4 + formaldehyde + reduced acceptor
Other name(s): KDM1 (gene name); LSD1 (gene name); lysine-specific histone demethylase 1
Systematic name: [histone H3]-N6,N6-dimethyl-L-lysine4:acceptor oxidoreductase (demethylating)
Comments: The enzyme specifically removes methyl groups from mono- and dimethylated lysine4 of histone 3. During the reaction the substrate is oxidized by the FAD cofactor of the enzyme to generate the corresponding imine, which is subsequently hydrolysed in the form of formaldehyde.The enzyme is similar to flavin amine oxidases, and differs from all other known histone lysine demethylases, which are iron(II)- and 2-oxoglutarate-dependent dioxygenases. The physiological electron acceptor is not known with certainty. In vitro the enzyme can use oxygen, which is reduced to hydrogen peroxide, but generation of hydrogen peroxide in the chromatin environment is unlikely as it will result in oxidative damage of DNA.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Forneris, F., Binda, C., Vanoni, M.A., Mattevi, A. and Battaglioli, E. Histone demethylation catalysed by LSD1 is a flavin-dependent oxidative process. FEBS Lett. 579 (2005) 2203–2207. [PMID: 15811342]
2.  Forneris, F., Battaglioli, E., Mattevi, A. and Binda, C. New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin. FEBS J. 276 (2009) 4304–4312. [PMID: 19624733]
[EC 1.14.99.66 created 2019]
 
 
EC 2.2.1.5     
Accepted name: 2-hydroxy-3-oxoadipate synthase
Reaction: 2-oxoglutarate + glyoxylate = 2-hydroxy-3-oxoadipate + CO2
For diagram of reaction mechanism, click here
Glossary: thiamine diphosphate = 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-diphosphoethyl)-4-methyl-1,3-thiazolium
Other name(s): 2-hydroxy-3-oxoadipate glyoxylate-lyase (carboxylating); α-ketoglutaric-glyoxylic carboligase; oxoglutarate: glyoxylate carboligase
Systematic name: 2-oxoglutarate:glyoxylate succinaldehydetransferase (decarboxylating)
Comments: The bacterial enzyme requires thiamine diphosphate. The product decarboxylates to 5-hydroxy-4-oxopentanoate. The enzyme can decarboxylate 2-oxoglutarate. Acetaldehyde can replace glyoxylate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9054-72-2
References:
1.  Schlossberg, M.A., Bloom, R.J., Richert, D.A. and Westerfield, W.W. Carboligase activity of α-ketoglutarate dehydrogenase. Biochemistry 9 (1970) 1148–1153. [PMID: 5418712]
2.  Schlossberg, M.A., Richert, D.A., Bloom, R.J. and Westerfield, W.W. Isolation and identification of 5-hydroxy-4-ketovaleric acid as a product of α-ketoglutarate: glyoxylate carboligase. Biochemistry 7 (1968) 333–337. [PMID: 4320439]
3.  Stewart, P.R. and Quayle, J.R. The synergistic decarboxylation of glyoxalate and 2-oxoglutarate by an enzyme system from pig-liver mitochondria. Biochem. J. 102 (1967) 885–897. [PMID: 16742506]
[EC 2.2.1.5 created 1972 as EC 4.1.3.15, transferred 2002 to EC 2.2.1.5]
 
 
EC 2.2.1.9     
Accepted name: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase
Reaction: isochorismate + 2-oxoglutarate = 5-enolpyruvoyl-6-hydroxy-2-succinyl-cyclohex-3-ene-1-carboxylate + CO2
Other name(s): SEPHCHC synthase; MenD
Systematic name: isochorismate:2-oxoglutarate 4-oxopentanoatetransferase (decarboxylating)
Comments: Requires Mg2+ for maximal activity. This enzyme is involved in the biosynthesis of vitamin K2 (menaquinone). In most anaerobes and all Gram-positive aerobes, menaquinone is the sole electron transporter in the respiratory chain and is essential for their survival. It had previously been thought that the products of the reaction were (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate (SHCHC), pyruvate and CO2 but it is now known that two separate enzymes are involved: this enzyme and EC 4.2.99.20, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase. Under basic conditions, the product can spontaneously lose pyruvate to form SHCHC.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 1112282-73-1
References:
1.  Jiang, M., Cao, Y., Guo, Z.F., Chen, M., Chen, X. and Guo, Z. Menaquinone biosynthesis in Escherichia coli: identification of 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate as a novel intermediate and re-evaluation of MenD activity. Biochemistry 46 (2007) 10979–10989. [DOI] [PMID: 17760421]
[EC 2.2.1.9 created 2008 (EC 2.5.1.64 created 2003, part-incorporated 2008)]
 
 
EC 2.3.1.61     
Accepted name: dihydrolipoyllysine-residue succinyltransferase
Reaction: succinyl-CoA + enzyme N6-(dihydrolipoyl)lysine = CoA + enzyme N6-(S-succinyldihydrolipoyl)lysine
For diagram of the citric-acid cycle, click here and for diagram of oxo-acid dehydrogenase complexes, click here
Glossary: dihydrolipoyl group
Other name(s): dihydrolipoamide S-succinyltransferase; dihydrolipoamide succinyltransferase; dihydrolipoic transsuccinylase; dihydrolipolyl transsuccinylase; dihydrolipoyl transsuccinylase; lipoate succinyltransferase (Escherichia coli); lipoic transsuccinylase; lipoyl transsuccinylase; succinyl-CoA:dihydrolipoamide S-succinyltransferase; succinyl-CoA:dihydrolipoate S-succinyltransferase; enzyme-dihydrolipoyllysine:succinyl-CoA S-succinyltransferase
Systematic name: succinyl-CoA:enzyme-N6-(dihydrolipoyl)lysine S-succinyltransferase
Comments: A multimer (24-mer) of this enzyme forms the core of the multienzyme complex, and binds tightly both EC 1.2.4.2, oxoglutarate dehydrogenase (succinyl-transferring) and EC 1.8.1.4, dihydrolipoyl dehydrogenase. The lipoyl group of this enzyme is reductively succinylated by EC 1.2.4.2, and the only observed direction catalysed by EC 2.3.1.61 is that where this succinyl group is passed to coenzyme A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9032-28-4
References:
1.  Derosier, D.J., Oliver, R.M. and Reed, L.J. Crystallization and preliminary structural analysis of dihydrolipoyl transsuccinylase, the core of the 2-oxoglutarate dehydrogenase complex. Proc. Natl. Acad. Sci. USA 68 (1971) 1135–1137. [DOI] [PMID: 4942179]
2.  Reed, L.J. and Cox, D.J. Multienzyme complexes. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 1, Academic Press, New York, 1970, pp. 213–240.
3.  Knapp, J.E., Mitchell, D.T., Yazdi, M.A., Ernst, S.R., Reed, L.J. and Hackert, M.L. Crystal structure of the truncated cubic core component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex. J. Mol. Biol. 280 (1998) 655–668. [DOI] [PMID: 9677295]
4.  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 2.3.1.61 created 1978, modified 2003]
 
 
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, KEGG, MetaCyc, 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 2.3.1.182      
Transferred entry: (R)-citramalate synthase. Now classified as EC 2.3.3.21, (R)-citramalate synthase.
[EC 2.3.1.182 created 2007, deleted 2021]
 
 
EC 2.3.1.190     
Accepted name: acetoin dehydrogenase system
Reaction: acetoin + CoA + NAD+ = acetaldehyde + acetyl-CoA + NADH + H+
Other name(s): acetoin dehydrogenase complex; acetoin dehydrogenase enzyme system; AoDH ES; acetoin dehydrogenase
Systematic name: acetyl-CoA:acetoin O-acetyltransferase
Comments: Requires thiamine diphosphate. It belongs to the 2-oxoacid dehydrogenase system family, which also includes EC 1.2.1.104, pyruvate dehydrogenase system, EC 1.2.1.105, 2-oxoglutarate dehydrogenase system, EC 1.2.1.25, branched-chain α-keto acid dehydrogenase system, and EC 1.4.1.27, glycine cleavage system. With the exception of the glycine cleavage system, which contains 4 components, the 2-oxoacid dehydrogenase systems share a common structure, consisting of three main components, namely a 2-oxoacid dehydrogenase (E1), a dihydrolipoamide acyltransferase (E2), and dihydrolipoamide dehydrogenase (E3).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Priefert, H., Hein, S., Kruger, N., Zeh, K., Schmidt, B. and Steinbuchel, A. Identification and molecular characterization of the Alcaligenes eutrophus H16 aco operon genes involved in acetoin catabolism. J. Bacteriol. 173 (1991) 4056–4071. [DOI] [PMID: 2061286]
2.  Oppermann, F.B. and Steinbuchel, A. Identification and molecular characterization of the aco genes encoding the Pelobacter carbinolicus acetoin dehydrogenase enzyme system. J. Bacteriol. 176 (1994) 469–485. [DOI] [PMID: 8110297]
3.  Kruger, N., Oppermann, F.B., Lorenzl, H. and Steinbuchel, A. Biochemical and molecular characterization of the Clostridium magnum acetoin dehydrogenase enzyme system. J. Bacteriol. 176 (1994) 3614–3630. [DOI] [PMID: 8206840]
4.  Huang, M., Oppermann, F.B. and Steinbuchel, A. Molecular characterization of the Pseudomonas putida 2,3-butanediol catabolic pathway. FEMS Microbiol. Lett. 124 (1994) 141–150. [DOI] [PMID: 7813883]
5.  Huang, M., Oppermann-Sanio, F.B. and Steinbuchel, A. Biochemical and molecular characterization of the Bacillus subtilis acetoin catabolic pathway. J. Bacteriol. 181 (1999) 3837–3841. [DOI] [PMID: 10368162]
[EC 2.3.1.190 created 2010, modified 2020]
 
 
EC 2.3.3.4     
Accepted name: decylhomocitrate synthase
Reaction: dodecanoyl-CoA + H2O + 2-oxoglutarate = (3S,4S)-3-hydroxytetradecane-1,3,4-tricarboxylate + CoA
For diagram of reaction, click here
Other name(s): 2-decylhomocitrate synthase; 3-hydroxytetradecane-1,3,4-tricarboxylate 2-oxoglutarate-lyase (CoA-acylating)
Systematic name: dodecanoyl-CoA:2-oxoglutarate C-dodecanoyltransferase (thioester-hydrolysing, 1-carboxyundecyl-forming)
Comments: Decanoyl-CoA can act instead of dodecanoyl-CoA, but 2-oxoglutarate cannot be replaced by oxaloacetate or pyruvate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 51845-40-0
References:
1.  Maahlén, A. Purification and some properties of 2-decylhomocitrate synthase from Penicillium spiculisporum. Eur. J. Biochem. 38 (1973) 32–39. [DOI] [PMID: 4774124]
2.  Brandäge, S., Dahlman, O., Lindqvist, B., Maahlén, A. and Mörch, L. Absolute configuration and enantiospecific synthesis of spiculisporic acid. Acta Chem. Scand. 38B (1984) 837–844.
[EC 2.3.3.4 created 1976 as EC 4.1.3.29, transferred 2002 to EC 2.3.3.4]
 
 
EC 2.3.3.5     
Accepted name: 2-methylcitrate synthase
Reaction: propanoyl-CoA + H2O + oxaloacetate = (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate + CoA
For diagram of reaction, click here
Glossary: 2-methylcitrate = (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate
Other name(s): 2-methylcitrate oxaloacetate-lyase; MCS; methylcitrate synthase; methylcitrate synthetase
Systematic name: propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming)
Comments: The enzyme acts on acetyl-CoA, propanoyl-CoA, butanoyl-CoA and pentanoyl-CoA. The relative rate of condensation of acetyl-CoA and oxaloacetate is 140% of that of propanoyl-CoA and oxaloacetate, but the enzyme is distinct from EC 2.3.3.1, citrate (Si)-synthase. Oxaloacetate cannot be replaced by glyoxylate, pyruvate or 2-oxoglutarate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 57827-78-8
References:
1.  Uchiyama, H. and Tabuchi, T. Properties of methylcitrate synthase from Candida lipolytica. Agric. Biol. Chem. 40 (1976) 1411–1418.
2.  Textor, S., Wendisch, V.F., De Graaf, A.A., Muller, U., Linder, M.I., Linder, D. and Buckel, W. Propionate oxidation in Escherichia coli: evidence for operation of a methylcitrate cycle in bacteria. Arch. Microbiol. 168 (1997) 428–436. [PMID: 9325432]
3.  Horswill, A.R. and Escalante-Semerena, J.C. Salmonella typhimurium LT2 catabolizes propionate via the 2-methylcitric acid cycle. J. Bacteriol. 181 (1999) 5615–5623. [PMID: 10482501]
4.  Brock, M., Maerker, C., Schütz, A., Völker, U. and Buckel, W. Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase. Eur. J. Biochem. 269 (2002) 6184–6194. [DOI] [PMID: 12473114]
5.  Domin, N., Wilson, D. and Brock, M. Methylcitrate cycle activation during adaptation of Fusarium solani and Fusarium verticillioides to propionyl-CoA-generating carbon sources. Microbiology 155 (2009) 3903–3912. [DOI] [PMID: 19661181]
[EC 2.3.3.5 created 1978 as EC 4.1.3.31, transferred 2002 to EC 2.3.3.5, modified 2015]
 
 
EC 2.3.3.14     
Accepted name: homocitrate synthase
Reaction: acetyl-CoA + H2O + 2-oxoglutarate = (2R)-2-hydroxybutane-1,2,4-tricarboxylate + CoA
For diagram of L-Lysine synthesis, click here
Glossary: (R)-homocitrate = (2R)-2-hydroxybutane-1,2,4-tricarboxylate
Other name(s): 2-hydroxybutane-1,2,4-tricarboxylate 2-oxoglutarate-lyase (CoA-acetylating); acetyl-coenzyme A:2-ketoglutarate C-acetyl transferase; homocitrate synthetase; HCS
Systematic name: acetyl-CoA:2-oxoglutarate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Comments: Belongs in the α-aminoadipate pathway of lysine synthesis, along with EC 4.2.1.36, homoaconitate hydratase. The enzyme also acts with oxaloacetate as substrate, but more slowly [2,3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9075-60-9
References:
1.  Strassman, M. and Ceci, L.N. Enzymatic formation of homocitric acid, an intermediate in lysine biosynthesis. Biochem. Biophys. Res. Commun. 14 (1964) 262–267. [DOI] [PMID: 5836514]
2.  Wulandari, A.P., Miyazaki, J., Kobashi, N., Nishiyama, M., Hoshino, T. and Yamane, H. Characterization of bacterial homocitrate synthase involved in lysine biosynthesis. FEBS Lett. 522 (2002) 35–40. [DOI] [PMID: 12095615]
3.  Andi, B., West, A.H. and Cook, P.F. Kinetic mechanism of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae. Biochemistry 43 (2004) 11790–11795. [DOI] [PMID: 15362863]
[EC 2.3.3.14 created 1972 as EC 4.1.3.21, transferred 2002 to EC 2.3.3.14]
 
 
EC 2.3.3.21     
Accepted name: (R)-citramalate synthase
Reaction: acetyl-CoA + pyruvate + H2O = CoA + (2R)-2-hydroxy-2-methylbutanedioate
Glossary: (2R)-2-hydroxy-2-methylbutanedioate = (2R)-2-methylmalate = (–)-citramalate
3-methyl-2-oxobutanoate = α-ketoisovalerate
2-oxobutanoate = α-ketobutyrate
4-methyl-2-oxopentanoate = α-ketoisocaproate
2-oxohexanoate = α-ketopimelate
2-oxoglutarate = α-ketoglutarate
Other name(s): CimA
Comments: One of the enzymes involved in a pyruvate-derived pathway for isoleucine biosynthesis that is found in some bacterial and archaeal species [1,2]. The enzyme can be inhibited by isoleucine, the end-product of the pathway, but not by leucine [2]. The enzyme is highly specific for pyruvate as substrate, as the 2-oxo acids 3-methyl-2-oxobutanoate, 2-oxobutanoate, 4-methyl-2-oxopentanoate, 2-oxohexanoate and 2-oxoglutarate cannot act as substrate [1,2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Howell, D.M., Xu, H. and White, R.H. (R)-citramalate synthase in methanogenic archaea. J. Bacteriol. 181 (1999) 331–333. [DOI] [PMID: 9864346]
2.  Xu, H., Zhang, Y., Guo, X., Ren, S., Staempfli, A.A., Chiao, J., Jiang, W. and Zhao, G. Isoleucine biosynthesis in Leptospira interrogans serotype 1ai strain 56601 proceeds via a threonine-independent pathway. J. Bacteriol. 186 (2004) 5400–5409. [DOI] [PMID: 15292141]
[EC 2.3.3.21 created 2007 as EC 2.3.1.182, transferred 2021 to EC 2.3.3.21]
 
 
EC 2.5.1.64      
Transferred entry: 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase. The reaction that was attributed to this enzyme is now known to be catalysed by two separate enzymes: EC 2.2.1.9 (2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase) and EC 4.2.99.20 (2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase)
[EC 2.5.1.64 created 2003, deleted 2008]
 
 


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