Iterative Methylation Leads to 3-Methylchuangxinmycin Production in <i>Actinoplanes tsinanensis</i> CPCC 200056.
Hu X, Shi Y, Jiang B, Fu J, Li X, Li S, Sun G, Ren W, Hu X, You X, Liu Z, Han X, Zhang T, Hong B, Wu L.
A new congener of chuangxinmycin (CM) was identified from <i>Actinoplanes tsinanensis</i> CPCC 200056. Its structure was determined as 3-methylchuangxinmycin (MCM) by 1D and 2D NMR. MCM could be generated <i>in vivo</i> from CM by heterologous expression of the vitamin B<sub>12</sub>-dependent radical SAM enzyme CxnA/A<sub>1</sub> responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A<sub>1</sub> could perform iterative methylation for MCM production. <i>In vitro</i> assays revealed significant activities of CM, DCM, and MCM against <i>Mycobacterium tuberculosis</i> H37Rv and clinically isolated isoniazid/rifampin-resistant <i>M. tuberculosis</i>, suggesting that CM and its derivatives may have potential for antituberculosis drug development.