Iterative Methylation Leads to 3-Methylchuangxinmycin Production in Actinoplanes tsinanensis CPCC 200056.

A new congener of chuangxinmycin (CM) was identified from CPCC 200056. Its structure was determined as 3-methylchuangxinmycin (MCM) by 1D and 2D NMR. MCM could be generated from CM by heterologous expression of the vitamin B-dependent radical SAM enzyme CxnA/A responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A could perform iterative methylation for MCM production. assays revealed significant activities of CM, DCM, and MCM against H37Rv and clinically isolated isoniazid/rifampin-resistant , suggesting that CM and its derivatives may have potential for antituberculosis drug development.