单位:[1]State Key Laboratory of Microbial Metabolism, School of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.[2]Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.[3]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education & Abiochem Biotech Joint Center for Pharmaceutical Innovation, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.[4]Department of Gastroenterology and Hepatology,Tongji Hospital affiliated to Huazhong University of Science and Technology,Wuhan 430071,China.内科学系消化内科华中科技大学同济医学院附属同济医院
Small-molecule carboxyl methyltransferases (CbMTs) constitute a small proportion of the reported methyltransferases, but they have received extensive attention due to their important physiological functions. Most of the small-molecule CbMTs isolated to date originate from plants and are members of the SABATH family. In this study, we identified a type of CbMT (OPCMT) from a group of Mycobacteria, which has a distinct catalytic mechanism from the SABATH methyltransferases. The enzyme contains a large hydrophobic substrate-binding pocket (~400 Å3) and utilizes two conserved residues, Thr20 and Try194, to retain the substrate in a favorable orientation for catalytic transmethylation. The OPCMT_like MTs have a broad substrate scope and can accept diverse carboxylic acids enabling efficient production of methyl esters. They are widely (more than 10,000) distributed in microorganisms, including several well-known pathogens, whereas no related genes are found in humans. In vivo experiments implied that the OPCMT_like MTs was indispensable for M. neoaurum, suggesting that these proteins have important physiological functions.
基金:
National
Key R&D Program of China (2021YFC2100600 to Z.L., 2018YFA0900400 to X.Q.),
the NSFC (31770063 to X.Q. and 22107069 to Z.L.).
第一作者单位:[1]State Key Laboratory of Microbial Metabolism, School of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.[2]Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.
共同第一作者:
通讯作者:
通讯机构:[1]State Key Laboratory of Microbial Metabolism, School of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.[2]Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.[3]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education & Abiochem Biotech Joint Center for Pharmaceutical Innovation, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
推荐引用方式(GB/T 7714):
Lin Zhi,Hu Zhiwei,Zhou Linjun,et al.A large conserved family of small-molecule carboxyl methyltransferases identified from microorganisms[J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2023,120(20):doi:10.1073/pnas.2301389120.
APA:
Lin Zhi,Hu Zhiwei,Zhou Linjun,Liu Benben,Huang Xiaowei...&Qu Xudong.(2023).A large conserved family of small-molecule carboxyl methyltransferases identified from microorganisms.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,120,(20)
MLA:
Lin Zhi,et al."A large conserved family of small-molecule carboxyl methyltransferases identified from microorganisms".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 120..20(2023)