2. Academic Validation
  3. Mutasynthesis of Antibacterial Halogenated Actinomycin Analogues

Mutasynthesis of Antibacterial Halogenated Actinomycin Analogues

  • J Nat Prod. 2021 Aug 27;84(8):2217-2225. doi: 10.1021/acs.jnatprod.1c00294.
Ziwei Yao 1 2 3,  Changli Sun 1 3,  Yuhui Xia 4,  Fang Wang 4,  Liwu Fu 4,  Junying Ma 1 3,  Qinglian Li 1 3,  Jianhua Ju 1 2 3
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, People's Republic of China.
  • 2 College of Oceanology, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, People's Republic of China.
  • 3 Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), No. 1119, Haibin Rd., Nansha District, Guangzhou 510301, People's Republic of China.
  • 4 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
PMID: 34270246 DOI: 10.1021/acs.jnatprod.1c00294
Abstract

Through precursor-directed biosynthesis, feeding halogenated (F-, Cl-, Br-, I-) or methoxy-substituted 4-methyl-3-hydroxyanthranilic acid (4-MHA) analogues to the acnGHLM-deleted mutant strain of Streptomyces costaricanus SCSIO ZS0073 led to the production of ten new actinomycin analogues (4-13). Several of the actinomycin congeners displayed impressive antimicrobial activities, with MIC values spanning 0.06-64 μg/mL to clinically derived Antibiotic resistant pathogens, including Staphylococcus aureus, Enterococcus faecium, and Candida albicans, with low cytotoxicity.

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