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Iterative Methylation Leads to 3-Methylchuangxinmycin Production in Actinoplanes tsinanensis CPCC 200056.
Hu, Xiaomin; Shi, Yuanyuan; Jiang, Bingya; Fu, Jie; Li, Xingxing; Li, Shufen; Sun, Guizhi; Ren, Weicong; Hu, Xinxin; You, Xuefu; Liu, Zhiyong; Han, Xingli; Zhang, Tianyu; Hong, Bin; Wu, Linzhuan.
Affiliation
  • Hu X; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Shi Y; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Jiang B; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Fu J; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Li X; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Li S; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Sun G; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Ren W; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Hu X; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • You X; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Liu Z; State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People's Republic of China.
  • Han X; State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People's Republic of China.
  • Zhang T; State Key Laboratory of Respiratory Disease, China-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People's Republic of China.
  • Hong B; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
  • Wu L; NHC Key Laboratory of Biotechnology of Antibiotics, and CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
J Nat Prod ; 86(1): 1-7, 2023 01 27.
Article in En | MEDLINE | ID: mdl-36649560
ABSTRACT
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 B12-dependent radical SAM enzyme CxnA/A1 responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A1 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.
Subject(s)

Full text: 1 Database: MEDLINE Main subject: Mycobacterium tuberculosis / Antitubercular Agents Language: En Year: 2023 Type: Article

Full text: 1 Database: MEDLINE Main subject: Mycobacterium tuberculosis / Antitubercular Agents Language: En Year: 2023 Type: Article