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 (...

Full description

Saved in:
Bibliographic Details
Published in:Organic process research & development 2019-09, Vol.23 (9), p.1813-1821
Main Authors: Chen, Qian, Xie, Baogang, Zhou, Liping, Sun, Lili, Li, Shanshan, Chen, Yuhan, Shi, Shan, Li, Yang, Yu, Mingan, Li, Wei
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.9b00004