Enzymatic C1 Conversion Group
The Enzymatic C1 Conversion Group has long been engaged in research in the fields of enzyme chemical biology and synthetic biology. Their focus has been on key scientific issues such as enzyme chemical mechanisms and enzyme molecular design in enzyme engineering and biocatalysis. They have conducted unique and original research, introducing the concept of dual functional molecule synergistic cytochrome P450 catalysis on an international level. Additionally, they have successfully constructed an artificial cytochrome P450 peroxidase catalytic system, which has been applied in the synthesis of chiral drug molecules. This breakthrough has opened up a new strategy of using exogenous small molecules to intervene in enzyme catalytic processes and regulate enzyme catalytic functions. The team believes that this approach can serve as a beneficial supplement to protein engineering technology and become a powerful tool for artificial enzyme molecular design. Recently, the team has proposed a new engineering method for P450 peroxidases in hydrogen peroxide channel engineering. This method successfully converts NADH dependent cytochrome P450 monooxygenases into peroxidases, significantly reducing the effective amount of hydrogen peroxide in the cytochrome P450 peroxidase system. This development is expected to lead to a universal enzyme engineering strategy for artificial cytochrome P450 peroxidases.
The research team is composed of one full-time researcher, one associate researcher, two research assistants, four doctoral students, and six master's students. These individuals come from diverse interdisciplinary backgrounds such as biochemistry and molecular biology, biotechnology, microbiology, pharmaceutical chemistry, and organic synthesis. The team has established extensive collaborations with well-known groups both domestically and internationally. Some of their partners include the Delft University of Technology in the Netherlands, the University of Dusseldorf in Germany, the University of Graz in Austria, Nagoya University in Japan, Shanxi University, Xiamen University, and the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences.
Institute's autonomous deployment of strong foundation plans, creation and reaction of new P450 enzymes, QIBEBT/SEI/QNESL S202302, 2023.05.01-2026.12.31, ¥ 5 million.
Ministry of Science and Technology national key research and development plan, key technology for the preparation of bio-based monomers, 2022YFC2104701, 2023.01.01-2025.12.31, ¥ 955,000.
National Natural Science Foundation general project, rational design and molecular mechanism research of steroid hydroxylation P450 monooxygenase based on hydrogen peroxide tunnel engineering, 32371311, 2024.01.01-2027.12.31, ¥ 500,000.
National Natural Science Foundation general project, molecular basis and evolutionary design of highly stable P450 monooxygenase, 21977104, 2020.01.01-2023.12.31, ¥ 660,000.
National Natural Science Foundation general project, rational design of P450 methane monooxygenase and its molecular mechanism research, 21778060, 2018.01.01-2021.12.31, ¥ 650,000.
Qingdao City Innovation Leading Talent Project, bio-pharmaceutical development based on cytochrome P450 enzymes, 18-1-2-9-zhc, 2018.01.01-2020.12.31, ¥ 1 million.
National Natural Science Foundation youth project, molecular design and reaction mechanism research of P450 peroxidase for direct nitration of alkenes, 22307125, 2024.01.01-2026.12.31, ¥ 300,000.
National Natural Science Foundation youth project, semi-rational design of novel artificial P450 monooxygenase co-factors guided by crystal structure, 22207112, 2023.01.01-2025.12.31, ¥ 300,000.
National Natural Science Foundation youth project, construction of carbon-hydrogen bond region and stereo-selective diverse P450 monooxygenase system and its molecular mechanism research, 22107105, 2022.01.01-2024.12.31, ¥ 300,000.
We possess several research platforms, including an enzyme mutation preparation and biochemical characterization platform, a structural biology platform, a computational simulation platform, an organic synthesis platform, and a whole cell preparation platform.
1. Qin, Xiangquan#; Jiang, Yiping#; Yao, Fuquan; Chen, Jie; Kong, Fanhui; Zhao, Panxia; Jin, Longyi*; Cong, Zhiqi*. Anchoring a Structurally Editable Proximal Cofactor-like Module to Construct an Artificial Dual-center Peroxygenase. Angew. Chem. Int. Ed Engl. 2023, e202311259. https://doi.org/10.1002/anie.202311259
2. Zhao, Panxia#; Kong, Fanhui#; Jiang, Yiping#; Qin, Xiangquan; Tian, Xiaoxia; Cong, Zhiqi*. Enabling Peroxygenase Activity in Cytochrome P450 Monooxygenases by Engineering Hydrogen Peroxide Tunnels. J. Am. Chem. Soc. 2023, 145, 9, 5506–5511. https://doi.org/10.1021/jacs.3c00195.
3. Wang, Xiling#; Lin, Xiaodan#; Jiang, Yiping#; Qin, Xiangquan#; Ma, Nana; Yao, Fuquan; Dong, Sheng; Liu, Chuanfei; Feng, Yingang; Jin, Longyi; Xian, Mo; Cong, Zhiqi*. Engineering Cytochrome P450BM3 Enzymes for Direct Nitration of Unsaturated Hydrocarbons. Angew. Chem. Int. Ed Engl. 2023, e202217678. https://doi.org/10.1002/anie.202217678
4. Chen, Jie#; Dong, Sheng#; Fang, Wenhan#; Jiang, Yiping; Chen, Zhifeng; Qin, Xiangquan; Wang, Cong; Zhou, Haifeng; Jin, Longyi; Feng, Yingang*; Wang, Binju*; Cong, Zhiqi*. Regiodivergent and Enantioselective Hydroxylation of C-H Bonds by Synergistic Use of Protein Engineering and Exogenous Dual-Functional Small Molecules. Angew. Chem. Int. Ed Engl. 2023, 62, e202215088. https://doi.org/10.1002/anie.202215088
5. Ma, Nana#; Chen, Zhifeng#; Chen, Jie#; Chen, Jingfei; Wang, Cong; Zhou, Haifeng;Yao, Lishan; Shoji, Osami; Watanabe, Yoshihito; Cong, Zhiqi*. Dual-Functional Small Molecules for Generating an Efficient Cytochrome P450BM3 Peroxygenase. Angew. Chem. Int. Ed. 2018, 57, 7628-7633. https://doi.org/10.1002/anie.201801592
