Abstract

Enzymes found in Nature perform incredible chemistry under mild reaction conditions and with high selectivity. Compared to traditional chemical strategies for manufacturing small molecules, enzymatic strategies have the potential to reduce waste, eliminate costly separation steps, and lower energy requirements. We combine expertise in biochemistry, biosynthesis, structural biology, and protein evolution to discover and to engineer enzymes for biocatalysis and chemical biology. In one project area, we use bioinformatics to identify and characterize unexplored nickel-dependent metalloenzymes, revealing entirely new enzymatic scaffolds as starting points for protein evolution. In another, we are developing a high-throughput platform to evolve enzymes for programmable, site-selective bioconjugation. We use evolution not only to develop useful tools for synthesis and biological discovery, but also to probe the basic mechanisms by which enzymes achieve selectivity in substrate recognition and reactivity.