BioChem - DOS

A tailor-made self-sufficient whole-cell biocatalyst enables scalable enantioselective synthesis of (R)-3-quinuclidinol in a high space-time yield

Organic process research & development

Chen, Qian; Xie, Baogang; Zhou, Liping; Sun, Lili; Li, Shanshan; Chen, Yuhan; Shi, Shan; Li, Yang; Yu, Mingan; Li, Wei

<P>A self-sufficient two-in-one whole-cell biocatalyst combining ketoreductase and cofactor regenerating enzyme activities has been developed and successfully utilized to synthesize (<I>R</I>)-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<SUP>-1</SUP>, and high space-time yield of (<I>R</I>)-3-quinuclidinol up to 1505.5 g L<SUP>-1</SUP> d<SUP>-1</SUP>, 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 (<I>R</I>)-3-quinuclidinol, essential for the production of solifenacin, revatropate, and aclidinium, with better clinical outcome than those currently available.</P><BR>[FIG OMISSION]</BR>

2019

American Chemical Society

1083-6160

1520-586x

23

9

pp.1813-1821

10.1021/acs.oprd.9b00004

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART97870739

biocatalyst; (R)-3-quinuclidinol; bifunctional enzymes; self-sufficient; biotransformation