Rational design of short‐chain dehydrogenase/reductase for enantio‐complementary synthesis of chiral 1,2‐diols by successive hydroxymethylation and reduction of aldehydes

Abstract

Enantiopure 1,2‐diols are widely used in the production of pharmaceuticals, cosmetics, and functional materials as essential building blocks or bioactive compounds. Nevertheless, developing a mild, efficient and environmentally friendly biocatalytic route for manufacturing enantiopure 1,2‐diols from simple substrate remains a challenge. Here, we designed and realized a step‐wise biocatalytic cascade to access chiral 1,2‐diols starting from aromatic aldehyde and formaldehyde enabled by a newly mined benzaldehyde lyase from Sphingobium sp. combined with a pair of tailored‐made short‐chain dehydrogenase/reductase from Pseudomonas monteilii (PmSDR‐MuR and PmSDR‐MuS) capable of producing (R)‐ and (S)‐1‐phenylethane‐1,2‐diol with 99% ee. The planned biocatalytic cascade could synthesize a series of enantiopure 1,2‐diols with a broad scope (16 samples), excellent conversions (94%–99%), and outstanding enantioselectivity (up to 99% ee), making it an effective technique for producing chiral 1,2‐diols in a more environmentally friendly and sustainable manner.