9j56 | pdb_00009j56
Functional Investigation of the SAM-Dependent Methyltransferases Rdmb in Anthracycline Biosynthesis
Structural highlights
FunctionRDMB_STREF Involved in the biosynthesis of the anthracycline aclacinomycin which is an aromatic polyketide antibiotic that exhibits high cytotoxicity and is widely applied in the chemotherapy of a variety of cancers. In vivo and in vitro, RdmB catalyzes the removal of the carboxylic group from the C-10 position of 15-demethoxyaclacinomycin T coupled to hydroxylation at the same C-10 position. It could also catalyze the removal of the carboxylic group at the C-10 position of 15-demethoxy-epsilon-rhodomycin coupled to hydroxylation at the same C-10 position to yield rhodomycin B. The reaction catalyzes by RdmB is intriguing, since the enzyme does not use any of the cofactors usually associated with hydroxylases such as flavins and/or metal ions to activate molecular oxygen.[1] [2] Publication Abstract from PubMedA 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. Functional investigation of the SAM-dependent methyltransferase RdmB in anthracycline biosynthesis.,Sang M, Yang Q, Guo J, Feng P, Ma W, Zhang W Synth Syst Biotechnol. 2024 Sep 12;10(1):102-109. doi: , 10.1016/j.synbio.2024.09.002. eCollection 2025. PMID:39308748[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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