One‐Pot Biocatalytic Conversion of Chemically Inert Hydrocarbons into Chiral Amino Acids through Internal Cofactor and H2O2 Recycling

Chemically inert hydrocarbons are the primary feedstocks used in the petrochemical industry and can be converted into more intricate and valuable chemicals. However, two major challenges impede this conversion process: selective activation of C‐H bonds in hydrocarbons and systematic functionalization required to synthesize complex structures. To address these issues, we developed a multi‐enzyme cascade conversion system based on internal cofactor and H2O2 recycling to achieve the one‐pot deep conversion from heptane to chiral (S)‐2‐aminoheptanoic acid under mild conditions. First, a hydrogen‐borrowing‐cycle‐based NADH regeneration method and H2O2in situ generation and consumption strategy were applied to realize selective C‐H bond oxyfunctionalization, converting heptane into 2‐hydroxyheptanoic acid. Integrating subsequent reductive amination driven by the second hydrogen‐borrowing cycle, (S)‐2‐aminoheptanoic acid was finally accumulated at 4.57 mM with eep > 99%. Hexane, octane, 2‐methylheptane, and butylbenzene were also successfully converted into the corresponding chiral amino acids with eep > 99%. Overall, the conversion system employed internal cofactor and H2O2 recycling, with O2 as the oxidant and ammonium as the amination reagent to fulfill the enzymatic conversion from chemically inert hydrocarbons into chiral amino acids under environmentally friendly conditions, which is a highly challenging transformation in traditional organic synthesis.