ORGN 231 |
| Christopher Walsh, Biol Chem & Mol Pharmacol Department, Biol Chem & Mol Pharmacol Department, Harvard Medical School, 45 Shattuck Street, Boston, MA 02115 |
| In the biosynthesis of several classes of antibiotics sugars are attached to aglycone scaffolds by antibiotic-specific glycosyl transferases 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 crosslinked heptapeptide scaffold is sequentially glucosylated, then vancoaminylated by Gtf E and GtfD in vancomycin maturation while in chloroeremomycin assembly the same heptapeptide is glucosylated (GtfB), then epivancosaminylated at two distinct sites (GtfA, GtfC). The specificity and mechanism of these glycosyl transferases will be discussed. In novobiocin biosynthesis, three enzymes (NovM,P,N) are thought to act sequentially to transfer an L-noviosyl residue to the novobiocic acid aglycone (NovM), followed by 04 methylation (NovP) and 03 carbamoylation to produce the mature antibiotic structure, targeting the GyrB subunit of DNA Gyrase. Characterization of NovM and NovP activities will be discussed. |
|
Alfred Bader Award in Bioinorganic or Bioorganic Chemistry
1:45 PM-5:00 PM, Monday, March 24, 2003 Convention Center -- La Nouvelle Ballroom A/B, Oral
Division of Organic Chemistry |