Abstract by Josh Tseng
Chemistry and Biochemistry
A Radical Cyclization Reaction Catalyzed by a Computationally Redesigned Radical SAM Enzyme
Radical S-adenosylmethionine (SAM) enzymes catalyze a wide range of radical-mediated transformations of their substrates, transformations inaccessible to other types of enzymes. While enzyme redesign is becoming commonplace in industrial small molecule synthesis, radical SAM enzymes have yet to enter this arena. We use Rosetta to leverage the radical-generating ability of radical SAM enzymes to carry out stereospecific radical-mediated reactions on arbitrarily-chosen substrates. We account for dynamic protein motion (molecular dynamics, MD) during enzyme design. We also describe development of a bacterial in vivo selection system for any arbitrarily chosen enzymatic activity based on the idea of reassemble enzyme fragments.