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A large conserved family of small-molecule carboxyl methyltransferases identified from microorganisms

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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.
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关键词: biosynthesis small molecule carboxyl methyltransferases steroid Mycobacterium

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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.

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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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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.
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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.
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