Expanding the reaction scope of biological catalysts beyond the realm of enzymatic transformations occurring in nature can create new opportunities for the exploitation of biocatalysis for organic synthesis and sustainable chemistry. This lecture will present progress made by our group toward the design and application of engineered hemoproteins for catalyzing abiological carbene transfer reactions. These efforts have led to the development of efficient and stereoselective biocatalysts for the asymmetric construction of carbon-carbon and carbon-heteroatom bonds via carbene insertion into olefins, heteroatom-hydrogen bonds, C—H bonds, and carbonyls. These biocatalytic strategies enable the stereoselective synthesis of core motifs in drugs and bioactive natural products at the preparative scale and they can be integrated into chemoenzymatic scheme for the generation of structurally diverse and stereochemically rich scaffolds of high value for medicinal chemistry and natural product synthesis. Presentation of these results will be complemented with a discussion of our current understanding of the structural determinants of reactivity and stereoselectivity in this new class of ‘carbene transferases’.
