Abstract

The thiopeptide antibiotics, including thiostrepton, demonstrate potent activity against a number of Gram-positive bacterial pathogens. Although topical formulations are utilized in veterinary medicine, the development of a thiopeptide antibiotic into a clinically useful agent for human medicine has been hampered by the lipophilicity of these metabolites. The structural complexity of this family of metabolites is a barrier to the rapid synthesis of a large number of derivatives, and the construction of analogs has been restricted to those accessible through semisynthesis. The recent reports of the biosynthetic gene clusters of thiostrepton and other thiopeptides now opens the door to a biosynthetic engineering for analog generation. As part of achieving this goal, a more sophisticated understanding of the molecular mechanisms at play in generating the intricate thiopeptide scaffold will be essential. Progress in understanding the myriad of posttranslational modifications needed to convert the TsrA precursor peptide to thiostrepton and adaptation of that machinery for the production of engineered thiopeptides will be discussed.

Continental breakfast will be served.