The biocatalytic oxidative deamination of β-amino alcohols holds significant practical potential in kinetic resolution and/or deracemization process to access (R)-β-amino alcohols. This study exemplifies a notable instance of acquisition and utilization of this valuable oxidative deamination activity. Initially, the mutation N261M (M0) was identified to endow a native valine dehydrogenase with oxidative deamination activity toward a few (S)-β-amino alcohols. Subsequently, a phylogenetic analysis-guided, double-code saturation mutagenesis strategy was proposed to engineer M0's side-chain binding site. This strategy facilitated the substrate-specific evolution of M0, resulting in the creation of a panel of mutants (M1-M4) with noteworthy oxidative deamination activity toward structurally diverse (S)-β-amino alcohols. Using these engineered amine dehydrogenases, termed as β-amino alcohol dehydrogenases (β-AADHs), the complete kinetic resolution and even deracemization of a range of β-amino alcohols have been achieved. This work reports distinct biocatalysts and a synthetic strategy for the synthesis of enantiopure (R)-β-amino alcohols and offers an innovative approach for substrate-specificity engineering of enzymes.

Chiral cyclic β-hydroxy ketones represent key motifs in the production of natural products of biological interest. Although the molecules are structurally simple, they require cumbersome synthetic steps to get access to them and their synthesis remains a challenge in organic chemistry. In this report, we describe a straightforward approach to enantiomerically enriched (R)- and (S)-3-hydroxycyclopentanone 2a, (R)- and (S)-3-hydroxycyclohexanone 2b, and (R)- and (S)-3-hydroxycycloheptanone 2c involving a transesterification resolution of the racemates using whole cells of marine microorganisms as catalysts and vinyl acetate the acyl donor and solvent. Twenty-six strains from a wide collection of isolates from marine sediments were screened, and seven strains were found to markedly catalyze the resolution in an asymmetric fashion. Using the strain Serratia sp., (R)-2a was isolated in 27% yield with 92% ee and (S)-2a in 65% yield with 43% ee, corresponding to an E-value of 37; (R)-2b was isolated in 25% yield with 91% ee and (S)-2b in 67% yield with 39% ee, corresponding to an E-value of 40; and (R)-2c was isolated in 30% yield with 96% ee and (S)-2c in 63% yield with 63% ee, corresponding to an E-value of 75.