Rudi Fasan

ENGINEERED METALLOPROTEIN CATALYSTS FOR SELECTIVE GROUP TRANSFER REACTIONS

Our research group is interested in developing and investigating metalloprotein catalysts for synthetic applications, ranging from late-stage C—H functionalization to asymmetric carbon-carbon and carbon-heteroatom bond formation. A major goal of our laboratory is the exploration of cytochrome P450 catalysis and P450-mediated chemoenzymatic synthesis for selective transformation of unactivated C(sp³)―H bonds in organic molecules. This seminar will describe our progress toward developing systematic strategies to modulate, predict, and fine-tune the selectivity of these oxidation biocatalysts and leveraging them for the late-stage manipulation of complex natural products. Our group is also interested in expanding the reaction scope of biological catalysts beyond that encompassed by natural enzymes. The second part of the seminar will describe our progress toward the design and application of engineered metalloproteins for selective carbene transfer reactions. These efforts have created new opportunities for the exploitation of biocatalysis for the asymmetric construction of carbon-carbon and carbon-heteroatom bonds and the synthesis of pharmaceuticals and other high value compounds. Presentation of these results will be complemented with a discussion on our current understanding of the mechanism of these reactions and of key structural features that influence the reactivity and selectivity of these biocatalysts.