Biocatalytic asymmetric ring-opening of meso-epoxides to enantiopure cyclic trans-β-amino alcohols involving a key amine transaminase

Chiral cyclic beta-amino alcohols are vital building blocks for the synthesis of numerous pharmaceuticals and bioactive molecules. Asymmetric ring-opening of cyclic meso-epoxides is a straightforward and appealing method for their synthesis. However, developing an environmentally friendly and cost-effective approach for this process remains elusive. Herein, the synthesis of enantiomerically pure cyclic beta-amino alcohols through a fully biocatalytic asymmetric ring-opening of cyclic meso-epoxides is described. A novel amine transaminase (CepTA) from Capronia epimyces with comparable activity and excellent enantioselectivity toward small molecule cyclic alpha-hydroxy ketones was discovered and proved to be efficient on a wide range of substrates. Homology modelling, molecular docking, and molecular dynamics simulations were also performed to elucidate the highly efficient catalytic mechanisms of CepTA for small cyclic alpha-hydroxy ketones. The asymmetric ring-opening of cyclic meso-epoxides (4 ' j-k) was successfully achieved by using combined recombinant E. coli (SpEH-AnDDH-BsLDH) and E. coli (CepTA) resting cells, leading to the production of cyclic (1R,2R)-trans-beta-amino alcohols (1 ' j-k) up to 81.8% conversions and >99% ee. This study marks the first instance of achieving fully biocatalytic asymmetric ring-opening of meso-epoxides to chiral cyclic beta-amino alcohols, offering a novel pathway for the environmentally friendly synthesis of chiral cyclic beta-amino alcohols from readily available, cost-effective meso-epoxides.