Efficient and Recyclable Photobiocatalytic System via Cofactor Regeneration for Chiral Aryl Alcohol Synthesis

Integrating efficient enzyme catalysis and sustainable photocatalysis is considered an eco-friendly and promising approach for substance conversion. In this work, employing a highly selective ketoreductase and a metal-free photocatalyst covalent organic framework (COF), we rationally constructed a coimmobilized biocatalyzed artificial photosynthesis system mediated by cofactor regeneration for chiral alcohol synthesis. COFs (denoted as TTA-T 0 and TTA-T 2 ) were rapidly fabricated at a moderate condition for comparative studies, demonstrating that donor–acceptor (D–A) structural TTA-T 2 possessed superior photochemical activity by virtue of efficient intramolecular charge transfer. With 98.3% yield of NADH in 40 min, TTA-T 2 was applied to cascade an NADH-dependent ketoreductase Ch KRED20 for the asymmetric reduction of acetophenone, providing ( R )-1-phenylethanol in excellent enantioselectivity (ee > 99%). Further, TTA-T 2 and Ch KRED 2 0 were coimmobilized into a green matrix to achieve enzyme protection as well as efficient and convenient recycling of both the photocatalyst and the enzyme. After optimizing the loading amount and other coimmobilized parameters, this coimmobilized system achieved satisfactory compatibility and reusability, with more than 75% photobiocatalytic activity remaining after four batches of operation. This work highlights the potential advantages of COFs as tailorable photocatalysts, and the strategy of coimmobilizing enzymes and photocatalysts could be extended to other solar-driven fine chemical production and for the further development of efficient artificial photosynthesis.