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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 20; p. e2301389120
• Main Authors: Lin, Zhi, Hu, Zhiwei, Zhou, Linjun, Liu, Benben, Huang, Xiaowei, Deng, Zixin, Qu, Xudong
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.05.2023
• Subjects: Amino Acid Sequence; Biological Sciences; Carboxylic acids; Esters; Humans; Hydrophobicity; Methyltransferases - metabolism; Microorganisms; Physical Sciences; Physiology; Plants - metabolism; Substrates; Mycobacterium; small molecule carboxyl methyltransferases; biosynthesis; steroid
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2301389120

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 , which has a distinct catalytic mechanism from the SABATH methyltransferases. The enzyme contains a large hydrophobic substrate-binding pocket (~400 Å ) 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 , suggesting that these proteins have important physiological functions.