Iterative Methylation Leads to 3-Methylchuangxinmycin Production in Actinoplanes tsinanensis CPCC 200056.
Xiaomin HuYuanyuan ShiBingya JiangJie FuXingxing LiShufen LiGuizhi SunWeicong RenXinxin HuXuefu YouZhiyong LiuXingli HanTian-Yu ZhangBin HongLinzhuan WuPublished in: Journal of natural products (2023)
A new congener of chuangxinmycin (CM) was identified from Actinoplanes tsinanensis CPCC 200056. Its structure was determined as 3-methylchuangxinmycin (MCM) by 1D and 2D NMR. MCM could be generated in vivo from CM by heterologous expression of the vitamin B 12 -dependent radical SAM enzyme CxnA/A 1 responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A 1 could perform iterative methylation for MCM production. In vitro assays revealed significant activities of CM, DCM, and MCM against Mycobacterium tuberculosis H37Rv and clinically isolated isoniazid/rifampin-resistant M. tuberculosis , suggesting that CM and its derivatives may have potential for antituberculosis drug development.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- genome wide
- dna methylation
- magnetic resonance
- high resolution
- emergency department
- magnetic resonance imaging
- mass spectrometry
- gene expression
- human immunodeficiency virus
- binding protein
- human health
- electronic health record
- solid state
- contrast enhanced
- structure activity relationship