Prof. Steven Van Lanen, University of Kentucky

The discovery and biosynthesis of highly modified nucleosides inhibiting bacterial translocase I, a novel target for antibiotics

The rapid increase in multiple drug resistant bacteria has detrimentally impacted the clinical utility of several antibiotics, a problem that is compounded by the steady decline in the FDA approval of new antibacterial drugs. We have developed a screen aimed at identifying novel antibiotics that are inhibitors of a previously unexploited cellular target, bacterial translocase I, which is an essential enzyme involved in peptidoglycan cell wall biosynthesis. This screen has led to the discovery of several uridine-based nucleoside antibiotics produced by various actinomycetes. We have now identified the biosynthetic genes for five of these translocase I inhibitors, and our biochemical studies have unearthed several interesting features including an ATP-independent mechanism of amide bond formation and a novel glycosylation pathway. These results, along with how the biochemical knowledge has been utilized to generate novel analogues, will be presented.

Biochemistry Division Seminar Series

For more information contact Prof. Wendy Kelly (404-385-1154).