EC |
1.14.11.52 |
Accepted name: |
validamycin A dioxygenase |
Reaction: |
validamycin A + 2-oxoglutarate + O2 = validamycin B + succinate + CO2 |
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For diagram of validamycin biosynthesis, click here |
Glossary: |
validamycin A = (1R,2R,3S,4S,6R)-2,3-dihydroxy-6-(hydroxymethyl)-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}cyclohexyl β-D-glucopyranoside
validamycin B = (1R,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-6-(hydroxymethyl)-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}cyclohexyl β-D-glucopyranoside |
Other name(s): |
vldW (gene name) |
Systematic name: |
validamycin-A,2-oxoglutarate:oxygen oxidoreductase (6′-hydroxylating) |
Comments: |
The enzyme was characterized from the bacterium Streptomyces hygroscopicus subsp. limoneus. Requires Fe2+. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Almabruk, K.H., Asamizu, S., Chang, A., Varghese, S.G. and Mahmud, T. The α-ketoglutarate/Fe(II)-dependent dioxygenase VldW is responsible for the formation of validamycin B. ChemBioChem 13 (2012) 2209–2211. [DOI] [PMID: 22961651] |
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[EC 1.14.11.52 created 2016] |
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EC |
2.4.1.338 |
Accepted name: |
validoxylamine A glucosyltransferase |
Reaction: |
UDP-α-D-glucose + validoxylamine A = UDP + validamycin A |
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For diagram of validamycin biosynthesis, click here |
Glossary: |
validoxylamine A = (1S,2S,3R,6S)-4-(hydroxymethyl)-6-{[(1S,2S,3S,4R,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)cyclohexyl]amino}cyclohex-4-ene-1,2,3-triol |
Other name(s): |
vldK (gene name); valG (gene name) |
Systematic name: |
UDP-α-D-glucose:validoxylamine-A 4′-O-glucosyltransferase |
Comments: |
The enzyme, characterized from the bacterium Streptomyces hygroscopicus subsp. limoneus, catalyses the ultimate step in the biosynthesis of the antifungal agent validamycin A. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Bai, L., Li, L., Xu, H., Minagawa, K., Yu, Y., Zhang, Y., Zhou, X., Floss, H.G., Mahmud, T. and Deng, Z. Functional analysis of the validamycin biosynthetic gene cluster and engineered production of validoxylamine A. Chem. Biol. 13 (2006) 387–397. [DOI] [PMID: 16632251] |
2. |
Xu, H., Minagawa, K., Bai, L., Deng, Z. and Mahmud, T. Catalytic analysis of the validamycin glycosyltransferase (ValG) and enzymatic production of 4′′-epi-validamycin A. J Nat Prod 71 (2008) 1233–1236. [DOI] [PMID: 18563934] |
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[EC 2.4.1.338 created 2016] |
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EC |
2.5.1.135 |
Accepted name: |
validamine 7-phosphate valienyltransferase |
Reaction: |
GDP-valienol + validamine 7-phosphate = validoxylamine A 7′-phosphate + GDP |
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For diagram of validamycin biosynthesis, click here |
Glossary: |
valienol = (1S,2S,3S,4R)-5-(hydroxymethyl)cyclohex-5-ene-1,2,3,4-tetrol
validamine = (1R,2S,3S,4S,6R)-4-amino-6-(hydroxymethyl)cyclohexane-1,2,3-triol |
Other name(s): |
vldE (gene name); valL (gene name) |
Systematic name: |
GDP-valienol:validamine 7-phosphate valienyltransferase |
Comments: |
The enzyme, characterized from several Streptomyces strains, is involved in the biosynthesis of the antifungal agent validamycin A. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Asamizu, S., Yang, J., Almabruk, K.H. and Mahmud, T. Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis. J. Am. Chem. Soc. 133 (2011) 12124–12135. [DOI] [PMID: 21766819] |
2. |
Zheng, L., Zhou, X., Zhang, H., Ji, X., Li, L., Huang, L., Bai, L. and Zhang, H. Structural and functional analysis of validoxylamine A 7′-phosphate synthase ValL involved in validamycin A biosynthesis. PLoS One 7:e32033 (2012). [DOI] [PMID: 22384130] |
3. |
Cavalier, M.C., Yim, Y.S., Asamizu, S., Neau, D., Almabruk, K.H., Mahmud, T. and Lee, Y.H. Mechanistic insights into validoxylamine A 7′-phosphate synthesis by VldE using the structure of the entire product complex. PLoS One 7:e44934 (2012). [DOI] [PMID: 23028689] |
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[EC 2.5.1.135 created 2016] |
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EC |
2.7.7.91 |
Accepted name: |
valienol-1-phosphate guanylyltransferase |
Reaction: |
GTP + valienol 1-phosphate = diphosphate + GDP-valienol |
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For diagram of validamycin biosynthesis, click here |
Glossary: |
valienol 1-phosphate = (1S,4R,5S,6R)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl phosphate |
Other name(s): |
vldB (gene name) |
Systematic name: |
GTP:valienol 1-phosphate guanylyltransferase |
Comments: |
The enzyme, characterized from the bacterium Streptomyces hygroscopicus subsp. limoneus, is involved in the biosynthesis of the antifungal agent validamycin A. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Yang, J., Xu, H., Zhang, Y., Bai, L., Deng, Z. and Mahmud, T. Nucleotidylation of unsaturated carbasugar in validamycin biosynthesis. Org. Biomol. Chem. 9 (2011) 438–449. [DOI] [PMID: 20981366] |
2. |
Asamizu, S., Yang, J., Almabruk, K.H. and Mahmud, T. Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis. J. Am. Chem. Soc. 133 (2011) 12124–12135. [DOI] [PMID: 21766819] |
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[EC 2.7.7.91 created 2016] |
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EC |
3.1.3.101 |
Accepted name: |
validoxylamine A 7′-phosphate phosphatase |
Reaction: |
validoxylamine A 7′-phosphate + H2O = validoxylamine A + phosphate |
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For diagram of validamycin biosynthesis, click here |
Glossary: |
validoxylamine A = (1S,2S,3R,6S)-4-(hydroxymethyl)-6-{[(1S,2S,3S,4R,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)cyclohexyl]amino}cyclohex-4-ene-1,2,3-triol |
Other name(s): |
vldH (gene name) |
Systematic name: |
validoxylamine-A 7′-phosphate phosphohydrolase |
Comments: |
The enzyme, characterized from the bacterium Streptomyces hygroscopicus subsp. limoneus, is involved in the biosynthesis of the antifungal agent validamycin A. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Asamizu, S., Yang, J., Almabruk, K.H. and Mahmud, T. Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis. J. Am. Chem. Soc. 133 (2011) 12124–12135. [DOI] [PMID: 21766819] |
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[EC 3.1.3.101 created 2016] |
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EC |
4.2.3.152 |
Accepted name: |
2-epi-5-epi-valiolone synthase |
Reaction: |
α-D-sedoheptulopyranose 7-phosphate = 2-epi-5-epi-valiolone + phosphate |
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For diagram of valiolone biosynthesis, click here |
Glossary: |
2-epi-5-epi-valiolone = (2S,3S,4S,5R)-2,3,4,5-tetrahydroxy-5-(hydroxymethyl)cyclohexan-1-one |
Other name(s): |
AcbC; ValA; CetA; SalQ; C7-cyclitol synthase |
Systematic name: |
α-D-sedoheptulopyranose-7-phosphate phosphate-lyase (cyclizing; 2-epi-5-epi-valiolone-forming) |
Comments: |
The enzyme is highly specific for α-D-sedoheptulopyranose 7-phosphate. It requires a divalent metal ion (Zn2+ or Co2+) and an NAD+ cofactor, which is transiently reduced during the reaction. The enzyme is involved in the biosynthesis of C7N-aminocyclitol natural products, such as the valienamine moiety of the antidiabetic drug acarbose and the crop protectant validamycin A. cf. EC 4.2.3.155, 2-epi-valiolone synthase and EC 4.2.3.154, demethyl-4-deoxygadusol synthase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Stratmann, A., Mahmud, T., Lee, S., Distler, J., Floss, H.G. and Piepersberg, W. The AcbC protein from Actinoplanes species is a C7-cyclitol synthase related to 3-dehydroquinate synthases and is involved in the biosynthesis of the α-glucosidase inhibitor acarbose. J. Biol. Chem. 274 (1999) 10889–10896. [DOI] [PMID: 10196166] |
2. |
Yu, Y., Bai, L., Minagawa, K., Jian, X., Li, L., Li, J., Chen, S., Cao, E., Mahmud, T., Floss, H.G., Zhou, X. and Deng, Z. Gene cluster responsible for validamycin biosynthesis in Streptomyces hygroscopicus subsp. jinggangensis 5008. Appl. Environ. Microbiol. 71 (2005) 5066–5076. [DOI] [PMID: 16151088] |
3. |
Wu, X., Flatt, P.M., Schlorke, O., Zeeck, A., Dairi, T. and Mahmud, T. A comparative analysis of the sugar phosphate cyclase superfamily involved in primary and secondary metabolism. ChemBioChem 8 (2007) 239–248. [DOI] [PMID: 17195255] |
4. |
Choi, W.S., Wu, X., Choeng, Y.H., Mahmud, T., Jeong, B.C., Lee, S.H., Chang, Y.K., Kim, C.J. and Hong, S.K. Genetic organization of the putative salbostatin biosynthetic gene cluster including the 2-epi-5-epi-valiolone synthase gene in Streptomyces albus ATCC 21838. Appl. Microbiol. Biotechnol. 80 (2008) 637–645. [DOI] [PMID: 18648803] |
5. |
Kean, K.M., Codding, S.J., Asamizu, S., Mahmud, T. and Karplus, P.A. Structure of a sedoheptulose 7-phosphate cyclase: ValA from Streptomyces hygroscopicus. Biochemistry 53 (2014) 4250–4260. [DOI] [PMID: 24832673] |
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[EC 4.2.3.152 created 2015, modified 2016] |
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