초록
<P>Enantiopure halohydrins, which are important building blocks for pharmaceutical agents, could be synthesized by biocatalytic reduction of α-halo ketones using ketoreductases. In this study, <I>Candida glabrata</I> ketoreductase 1 (CgKR1) variants with >99% stereoselectivity toward α-halo ketones, such as 2-chloroacetophenone, 2-chloro-4′-fluoroacetophenone, and 2-bromoacetophenone, were obtained through engineering of CgKR1 at residues Phe92 and Tyr208. Interestingly, asymmetric reduction of these α-halo ketones by all the variants of CgKR1 followed anti-Prelog’s rule, which is rarely found in natural ketoreductases. Moreover, the biocatalytic processes for reduction of these aromatic α-halo ketones with high substrate loading were achieved by coexpression of glucose dehydrogenase (GDH) for NADPH regeneration, indicating the potential of practical applications of these variants.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/accacs/2016/accacs.2016.6.issue-9/acscatal.6b01552/production/images/medium/cs-2016-01552q_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/cs6b01552'>ACS Electronic Supporting Info</A></P>