Amination of ω-Functionalized Aliphatic Primary Alcohols by a Biocatalytic Oxidation-Transamination Cascade

Amination of non-activated aliphatic fatty alcohols to the corresponding primary amines was achieved through a five-enzyme cascade reaction by coupling a long-chain alcohol oxidase from Aspergillus fumigatus (LCAO_Af) with a ω-transaminase from Chromobacterium violaceum (ω-TA_Cv). The alcohol was oxidized at the expense of molecular oxygen to yield the corresponding aldehyde, which was subsequently aminated by the PLP-dependent ω-TA to yield the final primary amine product. The overall cascade was optimized with respect to pH, O₂ pressure, substrate concentration, decomposition of H₂O₂ (derived from alcohol oxidation), NADH regeneration, and biocatalyst ratio. The substrate scope of this concept was investigated under optimized conditions by using terminally functionalized C₄-C₁₁ fatty primary alcohols bearing halogen, alkyne, amino, hydroxy, thiol, and nitrile groups.