Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Consecutive Methylation Catalyzed by TsrM, an Atypical Class B Radical SAM Methylase

Consecutive Methylation Catalyzed by TsrM, an Atypical Class B Radical SAM Methylase 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chinese Journal of Chemistry Wiley

Consecutive Methylation Catalyzed by TsrM, an Atypical Class B Radical SAM Methylase

Chinese Journal of Chemistry , Volume 40 (14) – Jul 15, 2022

Loading next page...
 
/lp/wiley/consecutive-methylation-catalyzed-by-tsrm-an-atypical-class-b-radical-5Q1BqDu8ou
Publisher
Wiley
Copyright
© 2022 SIOC, CAS, Shanghai, & WILEY‐VCH GmbH
eISSN
1614-7065
DOI
10.1002/cjoc.202200174
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Chinese Journal of ChemistryWiley

Published: Jul 15, 2022

Keywords: Biosynthesis; Biotransformations; Catalytic promiscuity; Enzyme; Methyltransferase

References