Enantioselective synthesis of enantiopure ß-amino alcohols via kinetic resolution and asymmetric reductive amination by a robust transaminase from Mycobacterium vanbaalenii.

ABSTRACT

Chiral ß-amino alcohols are very important chiral building block for preparing bioactive compounds for use in pharmaceutical and fine chemical industries. Synthesis of chiral ß-amino alcohols by transaminase is big challenging due to the strict substrate specificities and very low activity of the enzyme. In this work, a (R)-selective ω-transaminase (MVTA) from Mycobacterium vanbaalenii was employed as a biocatalyst for the first time for the synthesis of chiral ß-amino alcohol via kinetic resolution and asymmetric reductive amination. The enzyme was purified and characterized. Kinetic resolution of a set of racemic ß-amino alcohols including two cyclic ß-amino alcohols by MVTA was demonstrated, affording (R)-ß-amino alcohols, (1S, 2S)-trans-2-aminocyclopentanol and (1R, 2S)-cis-1-amino-2-indanols in >99% ee and 50-62% conversion. Asymmetric reductive amination of three α-hydroxy ketones (10-300 mM) by MVTA was conducted, (S)-ß-amino alcohols were obtained with >99% ee and 80-99% conversion. Preparation experiment for the reductive amination of 200 mM 2-hydroxyacetophenone by the resting cells of recombinant E. coli (MVTA) was proceeded smoothly and product (S)-2-amino-2-phenylethanol was obtained with 71% isolated yield, >99% ee and 68.6 g/L/d volumetric productivity. The current research proved that the MVTA is a robust enzyme for the preparation of chiral ß-amino alcohol with high volumetric productivity.