New Frontiers in Biocatlytic C-H Functionalization

Seminar series
Organic Colloquium
Thu, Jan 16 4:00pm
CS 76
Speaker Prof. Greg Challis
University of Warwick
Department of Chemistry

Abstract: C-H functionalization reactions are key steps in the biosynthesis of numerous bioactive natural products. Such reactions include hydroxylation, chlorination and desaturation of unactivated carbon centers, in addition to a range of oxidative heterocyclization reactions, exemplified by the conversion of the tripeptide ACV to the bicyclic penicillin nucleus.

In this lecture, the discovery and characterization of enzymes that catalyze a range of new or unusual C-H functionalization reactions in the biosynthesis of diverse natural products will be described. Examples include regio- and stereodivergent oxidative carbocyclisations by Rieske oxygenases in the biosynthesis of the antimalarial alkaloids streptorubin B and metacycloprodigiosin; cytochrome P450-catalysed nitration and hydroxylation reactions in the assembly of the EPA-approved herbicide thaxtomin A; flavoenzyme-mediated epoxyketone formation in the biosynthesis of the proteasome inhibitors TMC-86A and eponemycin; and thiazoline C-methylation by a radical-SAM methylase in watasemycin biosynthesis. Efforts to exploit these enzymes for industrially relevant biocatalysis and to create novel natural product analogues will also be described.