Mutasynthesis of Antibacterial Halogenated Actinomycin Analogues
Ziwei Yao, Changli Sun, Yuhui Xia, Fang Wang, Liwu Fu, Junying Ma, Qinglian Li, Jianhua Ju
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.
Topics & Concepts
Enterococcus faeciumCandida albicansAntimicrobialStaphylococcus aureusAntibioticsCytotoxicityMicrobiologyBacteriaMutantStreptomycesStereochemistryAntibacterial activityAntibacterial agentStrain (injury)Micrococcus luteusChemistryBiologyIn vitroBiochemistryGeneAnatomyGeneticsMicrobial Natural Products and BiosynthesisSynthesis and Biological ActivitySynthetic Organic Chemistry Methods