School Seminar: Professor Greg Challis, Monash University. “New frontiers in biocatalytic C-H functionalization”
Host: Prof Richard Payne
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 2-hydroxyphenylthiazoline biosynthesis. Efforts to exploit some of these enzymes for industrially relevant biocatalysis and to create novel natural product analogues will also be described.