Photobiocatalysis for Abiological Transformations

Harnessing biocatalysts for novel abiologicaltransformations is a longstanding goal of synthetic chemistry.Combining the merits of biocatalysis and photocatalysis allows forselective transformations fueled by visible light and offers manyadvantages including new reactivity, high enantioselectivity,greener syntheses, and high yields. Photoinduced electron orenergy transfer enables synthetic methodologies that complementconventional two electron processes or offer orthogonal pathwaysfor developing new reactions. Enzymes are well suited and can betuned by directed evolution to exert control over open-shellintermediates, thereby suppressing undesirable reactions anddelivering high chemo- and stereoselectivities. Within the pastdecade, the combination of biocatalysis and photocatalysis wasmainly focused on exploiting light-regenerated cofactors to function native enzymatic activity. However, recent developments havedemonstrated that the combination can unlock new-to-nature chemistry. Particularly, the discovery and application of new strategiesare well poised to expand the applications of photobiocatalysis. In the pastfive years, our lab has been studying the combinations of photocatalysis and biocatalysis that can be applied to create newsynthetic methodologies and solve challenges in synthetic organic chemistry. Our efforts have expanded the strategies for combiningexternal photocatalysts with enzymes through the construction of a synergistic cooperative stereoconvergent reduction systemconsisting of photosensitized energy transfer and ene-reductase-catalyzed alkene reduction. Additionally, our efforts have alsoextended the capability of cofactor-dependent photoenzymatic systems to include enantioselective bimolecular radicalhydroalkylations of alkenes by irradiating electron donor-acceptor complexes comprised of enzymatic redox active cofactors andunnatural substrates. In this Account, we highlight strategies developed by our group and others for combining biocatalysis and photocatalysis with theaim of introducing non-natural reactivity to enzymes. Presently, strategies applied to achieve this goal include the repurposing ofnatural photoenzymes, the elucidation of new photoreactivity within cofactor-dependent enzymes, the combination of externalphotocatalysts with enzymes, and the construction of artificial photoenzymes. By demonstrating the successful applications of thesestrategies for achieving selective new-to-nature transformations, we hope to spur interest in expanding the scope of photobiocatalyticsystems through the use and extension of these strategies and creation of new strategies. Additionally, we hope to elucidate theintuition in synergizing the unique capabilities of biocatalysis and photocatalysis so that photobiocatalysis can be recognized as apotential solution to difficult challenges in synthetic organic chemistry.

Automated summary

Combining biocatalysis and photocatalysis allows for selective transformations fueled by visible light and offers many advantages. Previous studies mainly focused on utilizing light-regenerated cofactors to function native enzymatic activity, but recent developments have demonstrated the potential for new chemistry. Our research has expanded the strategies for combining biocatalysis and photocatalysis through the construction of cooperative systems and the extension of cofactor-dependent photoenzymatic systems.