EC |
1.14.13.154 |
Accepted name: |
erythromycin 12-hydroxylase |
Reaction: |
erythromycin D + NADPH + H+ + O2 = erythromycin C + NADP+ + H2O |
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For diagram of erythromycin biosynthesis, click here |
Other name(s): |
EryK |
Systematic name: |
erythromycin-D,NADPH:oxygen oxidoreductase (12-hydroxylating) |
Comments: |
The enzyme is responsible for the C-12 hydroxylation of the macrolactone ring, one of the last steps in erythromycin biosynthesis. It shows 1200-1900-fold preference for erythromycin D over the alternative substrate erythromycin B [1]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Lambalot, R.H., Cane, D.E., Aparicio, J.J. and Katz, L. Overproduction and characterization of the erythromycin C-12 hydroxylase, EryK. Biochemistry 34 (1995) 1858–1866. [PMID: 7849045] |
2. |
Savino, C., Montemiglio, L.C., Sciara, G., Miele, A.E., Kendrew, S.G., Jemth, P., Gianni, S. and Vallone, B. Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate. J. Biol. Chem. 284 (2009) 29170–29179. [DOI] [PMID: 19625248] |
3. |
Montemiglio, L.C., Gianni, S., Vallone, B. and Savino, C. Azole drugs trap cytochrome P450 EryK in alternative conformational states. Biochemistry 49 (2010) 9199–9206. [DOI] [PMID: 20845962] |
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[EC 1.14.13.154 created 2012] |
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EC
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1.14.13.188
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Transferred entry: | 6-deoxyerythronolide B hydroxylase. Now EC 1.14.15.35, 6-deoxyerythronolide B hydroxylase
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[EC 1.14.13.188 created 2014, deleted 2018] |
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EC |
1.14.15.35 |
Accepted name: |
6-deoxyerythronolide B hydroxylase |
Reaction: |
6-deoxyerythronolide B + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 = erythronolide B + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O |
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For diagram of erythromycin biosynthesis, click here |
Other name(s): |
DEB hydroxylase; eryF (gene name); P450(eryF); CYP107A1 |
Systematic name: |
6-deoxyerythronolide-B,reduced ferredoxin:oxygen oxidoreductase |
Comments: |
A cytochrome P-450 (heme-thiolate) protein isolated from the bacterium Saccharopolyspora erythraea. The enzyme is involved in the biosynthesis of the antibiotic erythromycin. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Weber, J.M., Leung, J.O., Swanson, S.J., Idler, K.B. and McAlpine, J.B. An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Science 252 (1991) 114–117. [DOI] [PMID: 2011746] |
2. |
Shafiee, A. and Hutchinson, C.R. Macrolide antibiotic biosynthesis: isolation and properties of two forms of 6-deoxyerythronolide B hydroxylase from Saccharopolyspora erythraea (Streptomyces erythreus). Biochemistry 26 (1987) 6204–6210. [PMID: 2446657] |
3. |
Cupp-Vickery, J.R., Li, H. and Poulos, T.L. Preliminary crystallographic analysis of an enzyme involved in erythromycin biosynthesis: cytochrome P450eryF. Proteins 20 (1994) 197–201. [DOI] [PMID: 7846029] |
4. |
Nagano, S., Cupp-Vickery, J.R. and Poulos, T.L. Crystal structures of the ferrous dioxygen complex of wild-type cytochrome P450eryF and its mutants, A245S and A245T: investigation of the proton transfer system in P450eryF. J. Biol. Chem. 280 (2005) 22102–22107. [DOI] [PMID: 15824115] |
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[EC 1.14.15.35 created 2014 as EC 1.14.13.188, transferred 2018 to EC 1.14.15.35] |
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EC |
2.1.1.254 |
Accepted name: |
erythromycin 3′′-O-methyltransferase |
Reaction: |
(1) S-adenosyl-L-methionine + erythromycin C = S-adenosyl-L-homocysteine + erythromycin A
(2) S-adenosyl-L-methionine + erythromycin D = S-adenosyl-L-homocysteine + erythromycin B
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For diagram of erythromycin biosynthesis, click here |
Other name(s): |
EryG |
Systematic name: |
S-adenosyl-L-methionine:erythromycin C 3′′-O-methyltransferase |
Comments: |
The enzyme methylates the 3 position of the mycarosyl moiety of erythromycin C, forming the most active form of the antibiotic, erythromycin A. It can also methylate the precursor erythromycin D, forming erythromycin B, which is then converted to erythromycin A by EC 1.14.13.154, erythromycin 12 hydroxylase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Paulus, T.J., Tuan, J.S., Luebke, V.E., Maine, G.T., DeWitt, J.P. and Katz, L. Mutation and cloning of eryG, the structural gene for erythromycin O-methyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli. J. Bacteriol. 172 (1990) 2541–2546. [DOI] [PMID: 2185226] |
2. |
Summers, R.G., Donadio, S., Staver, M.J., Wendt-Pienkowski, E., Hutchinson, C.R. and Katz, L. Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production. Microbiology 143 (1997) 3251–3262. [DOI] [PMID: 9353926] |
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[EC 2.1.1.254 created 2012] |
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EC |
2.4.1.278 |
Accepted name: |
3-α-mycarosylerythronolide B desosaminyl transferase |
Reaction: |
dTDP-D-desosamine + 3-α-L-mycarosylerythronolide B = dTDP + erythromycin D
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For diagram of erythromycin biosynthesis, click here |
Glossary: |
dTDP-D-desosamine = dTDP-3,4,6-trideoxy-3-(dimethylamino)-α-D-xylo-hexopyranose
erythromycin D = (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-4-(2,6-dideoxy-3-C-methyl-α-L-ribo-hexopyranosyloxy)-14-ethyl-7,12-dihydroxy-6-[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyloxy]-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione
3-O-α-mycarosylerythronolide B = (3R,4S,5R,6R,7R,9R,11R,12S,13R,14R)-4-(2,6-dideoxy-3-C-methyl-α-L-ribo-hexopyranosyloxy)-14-ethyl-6,7,12-trihydroxy-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione |
Other name(s): |
EryCIII; dTDP-3-dimethylamino-4,6-dideoxy-α-D-glucopyranose:3-α-mycarosylerythronolide B 3-dimethylamino-4,6-dideoxy-α-D-glucosyltransferase |
Systematic name: |
dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose:3-α-mycarosylerythronolide B 3-dimethylamino-3,4,6-trideoxy-β-D-glucosyltransferase |
Comments: |
The enzyme is involved in erythromycin biosynthesis. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Yuan, Y., Chung, H.S., Leimkuhler, C., Walsh, C.T., Kahne, D. and Walker, S. In vitro reconstitution of EryCIII activity for the preparation of unnatural macrolides. J. Am. Chem. Soc. 127 (2005) 14128–14129. [DOI] [PMID: 16218575] |
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Lee, H.Y., Chung, H.S., Hang, C., Khosla, C., Walsh, C.T., Kahne, D. and Walker, S. Reconstitution and characterization of a new desosaminyl transferase, EryCIII, from the erythromycin biosynthetic pathway. J. Am. Chem. Soc. 126 (2004) 9924–9925. [DOI] [PMID: 15303858] |
3. |
Moncrieffe, M.C., Fernandez, M.J., Spiteller, D., Matsumura, H., Gay, N.J., Luisi, B.F. and Leadlay, P.F. Structure of the glycosyltransferase EryCIII in complex with its activating P450 homologue EryCII. J. Mol. Biol. 415 (2012) 92–101. [DOI] [PMID: 22056329] |
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[EC 2.4.1.278 created 2012, modified 2014] |
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