On August 26, the research article “One-Pot Biocatalytic Conversion of Chemically Inert Hydrocarbons into Chiral Amino Acids through Internal Cofactor and H₂O₂ Recycling” was published online in Angewandte Chemie International Edition. This study 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, which is a highly challenging transformation in traditional organic synthesis.

Hydrocarbons are the major constituents of crude oil and natural gas, the primary energy substances and essential feedstock for the petrochemical industry. The deep conversion and comprehensive utilization of petroleum/natural gas-derived hydrocarbons are important in achieving diversified molecular synthesis and expanding the petrochemical product landscape. Chiral amino acids are chemicals extensively applied in food, agricultural, pharmaceutical, cosmetic, and feedstuff industries. However, two significant challenges must be addressed: the functionalization of chemically inert and unpolarized C-H bonds under mild conditions and the design and construction of flexible and sustainable routes to effectively achieve these complicated conversions.

In this work, the researchers present a novel multi-enzyme cascade conversion system in which the chemically inert hydrocarbons were successfully converted to chiral amino acids with high optical purity under mild conditions. The multi-enzymatic deep conversion of heptane was employed as a model reaction. Driven by two cycles of hydrogen-borrowing and in situ generation of H₂O₂, the chemically inert heptane is converted to chiral (S)-aminoheptanoic acid with O₂ as an oxidant and ammonium as an amino group donor under ambient conditions.

The conversion from heptane to (S)-2-aminoheptanoic acid is realized through two successive functional modules. ModuleI is the two-step regioselective C-H bond oxyfunctionalization of heptane to produce 2-hydroxyheptanoic acid. The terminal and α-carbon C-H bonds were successively oxyfunctionalized to form carboxyl and hydroxyl groups. In module II, based on oxyfunctionalization, the researchers sought to introduce an amino group to α-carbon to achieve the conversion from 2-hydroxyheptanoic acid to 2-aminoheptanoic acid. The highest concentration of 2-aminoheptanoic acid reached 4.57 mM.

Motivated by the successful one-pot heptane-to-2-aminoheptanoic acid conversion, six aliphatic or aromatic hydrocarbons were further selected as starting substrates to synthesize chiral amino acids. Upon a 15-hour reaction, all of the chemically inert hydrocarbons were converted to their corresponding amino acids, except for 2-methylpentane. Remarkably, the ee_pvalues of all the produced chiral amino acids were > 99%.

The multi-enzyme cascade hydrocarbon deep conversion system developed in this study can comprehensively convert and utilize inert hydrocarbons from petroleum feedstock in an eco-friendly and gentle way. The challenging conversion was achieved with O2 from the air as the oxidant and inexpensive ammonium as the amination reagent. Additionally, the atom economy was improved by in-situgeneration and consumption of H₂O₂, eliminating the need for external H₂O₂. This system has the potential to outperform conventional organic synthesis methods and satisfy green chemistry requirements more effectively.