Regio- and stereo-selective amination of fatty acids to d-amino acids by a three-step one-pot cascade

Biocatalytic regio- and stereo-selective functionalization of renewable fatty acids for sustainable synthesis of value-added chiral chemicals is highly desirable but remains a great challenge. Herein, a three-step one-pot multienzyme cascade for the asymmetric synthesis of d-amino acids from renewable fatty acids was developed. Combination of P450 peroxygenase with two enantiocomplementary hydroxyacid oxidase(s) enabled the regioselective oxyfunctionalization of fatty acids into prochiral alpha-ketoacids with internal H2O2 recycling. An engineered d-amino acid dehydrogenase with formate dehydrogenase for self-recycling of the expensive cofactor NADPH was adopted for the reductive amination of alpha-ketoacids to d-amino acids. Various fatty acids (C-6-C-10) with different chain lengths can be efficiently converted into the corresponding d-amino acids with high yield (up to 99%) and excellent ee value (>99%). This study exploits the advantage of cascades and showcases the potential for synthesizing valuable chiral chemicals from inexpensive renewable feedstocks.