A Tailor-Made Self-Sufficient Whole-Cell Biocatalyst Enables Scalable Enantioselective Synthesis of (R)-3-Quinuclidinol in a High Space-Time Yield

A self-sufficient two-in-one whole-cell biocatalyst combining ketoreductase and cofactor regenerating enzyme activities has been developed and successfully utilized to synthesize (R)-3-quinuclidinol with an increase in the reaction rate of 3-fold over the native enzymes at low biocatalysts loading (-1.65%), excellent enantioselectivity, impressive substrate concentration of 486 g L–1, and high space-time yield of (R)-3-quinuclidinol up to 1505.5g L–1 d–1, which was the highest ever reported. These results demonstrated that the newly developed self-sufficient biocatalyst could be useful for synthetic and industrial application in synthesis of (R)-3-quinuclidinol, essential for the production of solifenacin, revatropate, and aclidinium, with better clinical outcome than those currently available.