Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols

Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely presented in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as byproduct, using NAD(P)H as cofactor under mild conditions, but hydroxy-ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19~99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9, the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model s-hydroxy ketone leading to the s-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.