Concurrent Linear Deracemization of Secondary Benzylic Alcohols via Simultaneous Photocatalysis and Whole-cell Biocatalysis.

Photobiocatalysis enables remarkable synthetic transformations by combining the exquisite stereoselectivity of enzymes with the mild generation of high-energy intermediates by photocatalysis, but practical applications remain limited due to enzyme photodamage. The deracemization of secondary alcohols is a key model reaction for photobiocatalytic protocols due to the importance of the enantioenriched products. However, current strategies rely on the temporal separation of catalytic cycles to circumvent incompatibilities, precluding photobiocatalytic transformations that require the generation of reactive intermediates. We report a single-step concurrent linear deracemization protocol by combining a water-soluble photocatalyst (sodium anthraquinone-2-sulfonate) with a promiscuous alcohol dehydrogenase ( acetophenone reductase) encapsulated in lyophilized microbial whole cells. Insights into enzyme selectivity and system dynamics from molecular docking and kinetic modeling guided the optimization of the multicomponent system. Our approach represents a modular and generalizable strategy for developing photobiocatalytic cascades operating under mutually compatible conditions, wherein spatial separation mitigates photodamage and enables simultaneous dual catalytic turnover.