Abstract

Natural products continue to inspire medicine, agriculture, and chemical biology through their remarkable structural diversity and biological activities. The biosynthesis of these molecules often relies on enzymes that catalyze chemically challenging transformations, yet how such unusual chemistry is programmed and controlled by proteins remains incompletely understood. In this seminar, I will describe our efforts to decode the unusual chemical logic of natural product biosynthesis and to harness biosynthetic enzymes as platforms for biocatalysis, including the discovery of unusual enzymes from the biosynthetic pathways of trichothecene, swainsonine, and loline alkaloids; as well as the reprograming of pyridoxal 5’-phosphate -dependent enzymes for [3+2] annulation reactions. Together, this work highlights how understanding natural product biosynthesis can enable both discovery of new bioactive compounds and the development of programmable biocatalysts for synthetic applications.