An enzyme-assembled gel monolithic microreactor for continuous flow asymmetric synthesis of aryl alcohols

Abstract

Green, efficient, and sustainable flow synthesis of intermediate chiral aryl alcohols is critical for continuous drug-manufacturing. Enzyme immobilization endows flow biocatalysis with higher application potential; however, conventional methods are limited by cumbersome operations, a trade-off between activity and stability, and low loading due to the required support. Here, for the first time, we demonstrated the microfluidic induction of alcohol dehydrogenase to form enzyme-assembled gels (EAGs) in a microreactor, with controllable mechanical properties and a porous architecture. Six chiral aryl alcohols were successfully synthesized by this approach in flow asymmetric reduction. Moreover, the support-free EAG was capable of in situ flow immobilization and reversible de-immobilization without reactor disassembly. The EAG monolithic microreactor presented an excellent space–time yield of 88.05 g L⁻¹ h⁻¹ and a high total turnover number of 62 600 after 100 h of operation (over 1300 reactor volumes), highlighting its high activity and stability.