Stereocomplementary bioreduction of β-ketonitrile without ethylated byproduct.

α-Ethylation is competing with the biocatalytic reduction of aromatic β-ketonitriles in a whole-cell system. Use of two newly mined robust and stereocomplementary carbonyl reductases in a biphasic system has completely eliminated the competing byproduct. For the first time, both enantiomers of fluoroxetine precursors were obtained at 0.5 M with >99% ee and excellent chemoselectivity, without addition of any external cofactors.