Theoretical research on the catalytic mechanism of metal dioxygenase in Fujian Institute of Technology has made progress

[ Instrument R&D of Instrument Network ] Oxygen activation and selective oxidative cracking of C–C bonds have great application value in organic synthesis and industrial production, and have always been a research hotspot in related chemical fields. Quercetin 2,4-dioxygenase (QueDs) is a typical class of biometal dioxygenases, because it can efficiently activate oxygen under mild conditions and catalyze the C of flavonol organic substrates with high selectivity –C bond oxidation ring-opening cracking, which has aroused extensive attention of experimental and theoretical chemists. Although the research on the QueDs system has continued for decades, the current understanding of QueDs catalytic reaction mechanism is still very controversial.

Li Chunsen's research group of the State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, with the support of key projects of the National Natural Science Foundation of China and the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences, etc., used a combination of QM/MM calculation methods and MD simulation methods for in-depth research. The wild-type nickel-containing quercetin 2,4-dioxygenase (Ni-QueD) and its Glu76Asp and Glu76Gln mutants catalyzed the whole process of oxidative degradation of quercetin, and found and clarified that Ni-QueD passes through the active center The Glu76 residue coordinated by the Ni atom adopts a proton-coupled electron transport process (PCET) to initiate the substrate oxidation reaction, and uses the hydrogen bonding interaction and conversion of Glu76 with the substrate to regulate the special oxidation ring-opening cleavage of the substrate. Reaction mechanism. This research work not only provides theoretical insights into the in-depth understanding of the use of key amino acid residues to regulate the catalytic activity of metalloenzymes, but also provides new ideas for the artificial synthesis of bionic catalysts similar to QueDs and the realization of specific catalytic reactions.

The above research results were published in the Journal of Catalysis (Journal of Catalysis, 2020, 387, 73-83) under the title of Mechanistic Insights into the Crucial Roles of Glu76 Residue in Nickel-dependent Quercetin 2,4-Dioxygenase for Quercetin Oxidative Degradation . DOI: 10.1016/j.jcat.2020.04.016), the first author of the article is Yan Xueyuan, a doctoral student at the University of Chinese Academy of Sciences.