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

Abstract

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 α-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 α-ketoacids to D-amino acids. Various fatty acids (C₆–C₁₀) 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.