Antibiotic glycosyltransferases

In the biosynthesis of several classes of antibiotics, sugars are attached to aglycone scaffolds by antibiotic-specific glycosyltransferases in the latter stages of the pathways. Two glycosylation pathways will be examined: the glycopeptide antibiotics of the vancomycin class and the aminocoumarin antibiotics of the novobiocin class. An oxidatively cross-linked heptapeptide scaffold is sequentially glucosylated and vancosaminylated by GtfE and GtfD, respectively, in vancomycin maturation, while in chloroeremomycin assembly the same heptapeptide is glucosylated by GtfB, then epivancosaminylated at two distinct sites by GtfA and GtfC. The specificity and mechanism of these glycosyltransferases will be discussed. In novobiocin biosynthesis, three enzymes (NovM, NovP and NovN) are thought to act sequentially to transfer an L-noviose moiety to the novobiocic acid aglycone (NovM), followed by 4′-hydroxyl methylation (NovP) and 3′-hydroxyl carbamoylation to produce the mature antibiotic structure, targeting the Gyr8 subunit of DNA gyrase. Initial characterization of NovM and NovP will be discussed.