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A Tailor-Made Self-Sufficient Whole-Cell Biocatalyst Enables Scalable Enantioselective Synthesis of (R)‑3-Quinuclidinol in a High Space-Time Yield
Ist Teil von
Organic process research & development, 2019-09, Vol.23 (9), p.1813-1821
Ort / Verlag
American Chemical Society
Erscheinungsjahr
2019
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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 1505.5 g 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.