Activation and\nStabilization of Engineered Amine Dehydrogenase\nby Fatty Acids for Bioprocess Intensification of Asymmetric Reductive\nAmination

In\nthis study, we present a significant advancement in\nthe field\nof enzymatic asymmetric reductive amination (ARA) of ketones, a pivotal\nreaction for chiral amine synthesis. Through a combination of semirational\nenzyme design and bioprocess development, we achieve the dual activation\nand stabilization of amine dehydrogenase (AmDH) to meet industrial\ndemands. The engineered AmDH exhibits remarkable catalytic efficiency\n(turnover number, TON >1,000,000) and exceptional stability (half-life\n>7 days at 50 °C), with a broadened substrate scope including\nvarious aryl alkyl ketones and fatty ketones. Leveraging biobased\noleic acid as an activator and stabilizer, we achieved kilogram-scale\nsynthesis of chiral amines. Furthermore, the integration of AmDH with\nchemical catalysts in chemoenzymatic cascades has enabled the synthesis\nof a wide array of pharmaceutically relevant amines from diverse substrates,\ndemonstrating the enzyme’s versatility and potential to transform\nsynthetic chemistry.