ABSTRACT: The Cytochromes P450 are heme-thiolate enzymes that carry out selective oxyfunctionalization of a wide range of substrates C-H bonds using molecular dioxygen and two reducing equivalents. Recent efforts have focused on the use of light-harvesting units to trigger P450 activity upon visible light excitation. Our laboratory has taken advantage of Ru(II)-diimine complexes and their unique excited properties to harness the P450 synthetic potential. The covalent attachment of these photosensitizers to non-native single cysteine residues has enabled rapid electron injections into the heme domain of several bacterial P450 enzymes leading to high photocatalytic activity and coupling efficiency. The crystal structure of the most efficient hybrid enzyme reveals that the photosensitizer is ideally positioned to deliver electrons to the heme active site utilizing the natural electron transfer pathway. A combination of rational and directed evolution approaches are currently employed to optimize the biocatalyst photocatalytic activity and expand the scope of the light-driven P450 activity. In addition, we recently sought to capitalize on the photoredox properties of these inorganic complexes combined with the P450 biocatalysis to develop novel chemoenzymatic approaches including selective light-driven trifluoromethylation/oxyfunctionalization of several substituted arenes.
BIO: Dr. Cheruzel completed his graduate work at the University of Louisville with Robert M. Buchanen. After completing a post-doctoral fellowship at the California Institute of Technology with Harry Gray in 2009, Dr. Cheruzel joined the faculty of the Department of Chemistry, at San Jose State University where he is an associate professor. His research interests span the development of hybrid P450 enzymes, photocatalytic chemistry, and the development of microspherical polymers.