Concise Report
Consecutive Methylation Catalyzed by TsrM, an Atypical Class B Radical SAM Methylase
Runze Wu,
Wei Ding,
Qi Zhang,
Runze Wu
Department of Chemistry, Fudan University, Shanghai, 200433 China
Search for more papers by this authorCorresponding Author
Wei Ding
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Qi Zhang
Department of Chemistry, Fudan University, Shanghai, 200433 China
E-mail: [email protected]; [email protected]Search for more papers by this authorRunze Wu,
Wei Ding,
Qi Zhang,
Runze Wu
Department of Chemistry, Fudan University, Shanghai, 200433 China
Search for more papers by this authorCorresponding Author
Wei Ding
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Qi Zhang
Department of Chemistry, Fudan University, Shanghai, 200433 China
E-mail: [email protected]; [email protected]Search for more papers by this authorComprehensive Summary
TsrM is a cobalamin-dependent radical S-adenosylmethionine (SAM) methyltransferase belonging to the Class B radical SAM methylase (RSM) family. This enzyme catalyzes the C-2 methylation of L-tryptophan to produce 2-methyltrytophan (2-MeTrp), an intermediate involved in the biosynthesis of thiostrepton A. In this work, we report characterization of an unexpected activity of TsrM, which carries out an additional methylation reaction on the product 2-MeTrp. A series of isotopic labeling studies and assays with different Trp analogs revealed that TsrM is able to transfer a methyl group from SAM to the C4 of 2-MeTrp to produce 2,4-dimethyltryptophan. These results reveal the intriguing substrate specificity of TsrM, further expanding the reaction promiscuity of the radical SAM superfamily enzymes.
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