초록
<P><I>t</I>-Butyl-6-cyano-(3<I>R</I>,5<I>R</I>)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (<I>Lb</I>CR) was newly identified from <I>Lactobacillus brevis</I>, which displays high activity and excellent diastereoselectivity toward bulky <I>t</I>-butyl 6-cyano-(5<I>R</I>)-hydroxy-3-oxo-hexanoate (<B>7</B>). The engineered <I>Escherichia coli</I> cells harboring <I>Lb</I>CR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate <B>7</B>. As a result, as much as 300 g L<SUP>–1</SUP> of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% <I>de</I> in a space–time yield of 351 g L<SUP>–1</SUP> d<SUP>–1</SUP>, indicating a great potential of <I>Lb</I>CR for practical synthesis of the very bulky and <I>bi</I>-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/oprdfk/2017/oprdfk.2017.21.issue-9/acs.oprd.7b00194/production/images/medium/op-2017-00194t_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/op7b00194'>ACS Electronic Supporting Info</A></P>