A strategy to identify a ketoreductase that preferentially synthesizes pharmaceutically relevant (S)-alcohols using whole-cell biotransformation

Table 2 Comparison of alcohol yields for commercially relevant ketones using six ketoreductases

Prochiral ketone	Alcohol yield (%)
Prochiral ketone	SsADH	ByeuD	FabG	Hketo	PAR	ZRK
Aprepitant ketone intermediate (compound 3)	0.8	7	0	1.32	0	22.6
Sitagliptin ketone intermediate (compound 8)	9.6	29	38	87	18	98
Dolastatin ketone intermediate (compound 6)	2.98	26	31.8	41	2	>99

ZRK was found to be the best catalyst among the chosen enzymes. The substrates used are as follows, aprepitant ketone intermediate: 1-(3,5-bis-trifluoromethyl-phenyl)-ethanone, Sitagliptin ketone intermediate: 3-oxo-4-(2,4,5-trifluoro-phenyl) butyric acid methyl ester and dolastatin ketone intermediate: 2-phenyl-1-thiazol-2-yl-ethanone

ISSN: 1475-2859