Talsaclidine fumarate

( R )‐3‐quinuclidinol is a pivotal chiral synthon for pharmaceuticals such as talsaclidine, revatropate, and solifenacin. Conventional chemical synthesis routes, however, suffer from inherent drawbacks including inefficient racemic resolution and dependence on costly chiral catalysts. In this study, a carbonyl reductase (CRs‐7) with high activity was selected from among 20 candidates and subsequently engineered through a machine learning‐assisted strategy integrated with molecular dynamics (MD) simulations. The optimal mutant, V167F/C171Y, displayed a 5.3‐fold enhancement in catalytic activity relative to the wild‐type enzyme. Structural and computational analyses revealed that the mutations remodel the architecture of the substrate‐access tunnel, resulting in reduced nucleophilic attack distances ( d 1 and d 2) and accelerated catalysis. Furthermore, the V167F/C171Y variant was applied in a 50‐L bioreactor, wherein only 7.50 g/L DCW (dry cell weight) of whole‐cell biocatalyst was required to completely convert 100 g/L substrate within 6 h, affording ( R )‐3‐quinuclidinol with >99% conversion and enantiomeric excess ( ee ). The exceptional biocatalytic performance, coupled with high substrate tolerance and operational stability, underscores the potential of this engineered enzyme for sustainable industrial manufacturing.