Title: Biocatalysis tools & strategies to enable complex molecule synthesis

Abstract: In Nature’s approach to building molecules, hundreds of different enzymes carry out their individual chemical reactions simultaneously in a single cell. The laboratory approach to chemical synthesis is very different. Modern medicines, dyes, fragrances, and biological probe compounds are prepared with combinations of small molecule reagents and catalysts that are significantly less effective than Nature at achieving multistep synthetic cascades. The work described leverages the power of Nature’s tools for building complex molecules to synthesize libraries of natural and unnatural products. Enzymes with potential synthetic utility are used as a starting point for engineering biocatalysts with (1) broad substrate scope, (2) high catalytic efficiency, and (3) exquisite substrate, site-, and stereoselectivity. These biocatalytic methods are employed to efficiently synthesize biologically active complex molecules in a high throughput format.