1. Functional investigation of the SAM-dependent methyltransferase RdmB in anthracycline biosynthesis
- Author
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Moli Sang, Qingyu Yang, Jiawei Guo, Peiyuan Feng, Wencheng Ma, and Wei Zhang
- Subjects
Methyltransferase ,Anthracyclines ,Biosynthesis ,Catalytic mechanism ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 - Abstract
A novel sub-class of S-adenosyl-l-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from Streptomyces purpurascens, it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4-O-methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4-O-methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.
- Published
- 2025
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