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Mechanistic studies of the biosynthesis of 2-thiosugar: evidence for the formation of an enzyme-bound 2-ketohexose intermediate in BexX-catalyzed reaction.

ABSTRACT: The first mechanistic insight into 2-thiosugar production in an angucycline-type antibiotic, BE-7585A, is reported. d-Glucose 6-phosphate was identified as the substrate for the putative thiosugar biosynthetic protein, BexX, by trapping the covalently bonded enzyme-substrate intermediate. The site-specific modification at K110 residue was determined by mutagenesis studies and LC-MS/MS analysis. A key intermediate carrying a keto functionality was confirmed to exist in the enzyme-substrate complex. These results suggest that the sulfur insertion mechanism in 2-thiosugar biosynthesis shares similarities with that for thiamin biosynthesis.

SUBMITTER: Sasaki E

PROVIDER: S-EPMC2975028 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Mechanistic studies of the biosynthesis of 2-thiosugar: evidence for the formation of an enzyme-bound 2-ketohexose intermediate in BexX-catalyzed reaction.

Sasaki Eita E Liu Hung-Wen HW

Journal of the American Chemical Society 20101101 44

The first mechanistic insight into 2-thiosugar production in an angucycline-type antibiotic, BE-7585A, is reported. d-Glucose 6-phosphate was identified as the substrate for the putative thiosugar biosynthetic protein, BexX, by trapping the covalently bonded enzyme-substrate intermediate. The site-specific modification at K110 residue was determined by mutagenesis studies and LC-MS/MS analysis. A key intermediate carrying a keto functionality was confirmed to exist in the enzyme-substrate comple ...[more]

PMID: 20961106

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