Research in the Jarrett Lab focuses on understanding the chemical mechanisms of reactions catalyzed by enzymes, with a particular focus on enzymes that employ organic radicals as reactive intermediates. Biotin synthase is a radical enzyme that adds a sulfur atom to complete the biosynthesis of this important cofactor; our work has shown that the enzyme uses S-adenosylmethionine to generate carbon radicals and adds a sulfur atom from an inorganic iron-sulfur cluster to these radicals to generate new carbon-sulfur bonds, a reaction that has no prior chemical or biochemical precedent. We are also working on the mechanisms of several related enzymes that generate sulfur-containing thioether crosslinks in peptide natural products. These enzymes generate a new product, 5’-deoxyadenosine, whose metabolism has not been fully elucidated. Our work has identified a novel catabolic pathway that includes promiscuous enzymes shared with the well-known methionine salvage pathway.
Fellow