Discovery and mechanisms of biosynthetic enzymes

PROJECT SUMMARY Biosynthetic pathways are rich in enzymatic transformations that produce structurally diverse natural products, such as secondary metabolites, modified nucleic acids, and modified peptides. Discovering and understanding the molecular basis for these transformations underpins efforts towards development of deep insights into factors that either belie many disease processes, or their use in development of therapeutic agents. The focus of the proposed studies will be elucidating the mechanisms of enzymes that employ radical transformations in effecting complex transformation in the biosynthesis of ribosomally produced and posttranslationally modified peptides. This application will make use of biochemical, structural, and spectroscopic techniques to probe the mechanisms of these enzymes, establish structure-function relationships, and to discover novel biosynthetic enzymes.