Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase

Photoenzymesare a rare class of biocatalysts that use light tofacilitate chemical reactions. Many of these catalysts utilize a flavincofactor to absorb light, suggesting that other flavoproteins mighthave latent photochemical functions. Lactate monooxygenase is a flavin-dependentoxidoreductase previously reported to mediate the photodecarboxylationof carboxylates to afford alkylated flavin adducts. While this reactionholds a potential synthetic value, the mechanism and synthetic utilityof this process are unknown. Here, we combine femtosecond spectroscopy,site-directed mutagenesis, and a hybrid quantum-classical computationalapproach to reveal the active site photochemistry and the role theactive site amino acid residues play in facilitating this decarboxylation.Light-induced electron transfer from histidine to flavin was revealed,which has not been reported in other proteins. These mechanistic insightsenable the development of catalytic oxidative photodecarboxylationof mandelic acid to produce benzaldehyde, a previously unknown reactionfor photoenzymes. Our findings suggest that a much wider range ofenzymes have the potential for photoenzymatic catalysis than has beenrealized to date.