Polyketides are a diverse class of natural products that possess a large assortment of biological activities and are used to treat many diseases. We utilize X-ray crystallography and structural analysis in parallel with biosynthesis, chemical biology, and computational biology to aid in our understanding of PKS enzyme machinery.

Polyketide intermediates are very reactive and cannot be isolated. Our lab uses atom replacement strategies to synthesize small molecule mimics of biosynthetic intermediates in order to better understand how enzymes handle highly reactive polyketides.

Fatty acids in E. coli are made by a set of enzymes called a type II fatty acid synthase. We utilize mechanism based crosslinking approaches to trap fatty acid biosynthesis in action and solve complex crystal structures.