초록
<P><B>Abstract</B></P> <P>The 3-hydroxypiperidine moiety is a privileged scaffold encountered in many bioactive compounds. An NADPH-dependent reductase (YGL039W) from <I>Kluyveromyces marxianus</I> ATCC 748 was isolated to show excellent catalytic activity in (<I>R</I>)-<I>N</I>-Boc-3-hydroxypiperidine [(<I>R</I>)-NBHP] production. Using a GDH-catalyzed cofactor-recycling system to ensure a sufficient supply of NADPH, the effects of temperature, pH, metal ions, substrate concentration, biocatalyst dosage, and cofactors on the YGL039W-catalyzed bioreduction were investigated and optimized. Finally, an extremely high concentration of <I>N</I>-Boc-piperidin-3-one (NBPO, 400g/L) could be completely reduced to (<I>R</I>)-NBHP (>99% <I>ee</I>), with a total turnover number of 20,000. This process shows significant potential for the industrial production of (<I>R</I>)-NBHP.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A carbonyl reductase was discovered to reduce NBPO to (<I>R</I>)-NBHP with high activity. </LI> <LI> A GDH-catalyzed cofactor-recycling system was used to regenerate NADPH. </LI> <LI> The process was optimized and applied to produce (<I>R</I>)-NBHP (>99% <I>ee</I>). </LI> <LI> The asymmetric reduction was conducted at high substrate loading (400g/L). </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>