Deletion of the accramycin pathway-specific regulatory gene <i>accJ</i> activates the production of unrelated polyketide metabolites

The manipulation of regulatory genes has been employed to awaken cryptic metabolites in Streptomyces. Of particular interest in recent years is the effect of disruption of a pathway-specific gene to other biosynthetic pathways. Herein, we report the inactivation of the accramycin pathway-specific regulatory gene, accJ in Streptomyces sp. MA37 resulted in the production of unrelated polyketide metabolites. Through detailed mass spectrometric and spectroscopic analyses, and comparison with literature data, their structures were deduced as 3-methoxy-2-methyl-4H-pyran-4-one (1), zanthopyranone (2), propioveratrone (3), and TW94a (4). To the best of our knowledge, this is the first report of the isolation of 1–3 from bacteria. Compounds 1, 2, and 4 showed weak to moderate activity against Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium. Propioveratrone (3) displayed better inhibitory activity (MIC = 6.3 μg/mL) than ampicillin against multi-drug resistant E. faecium K60–39 clinical isolate (MIC = 25 μg/mL), suggesting a promising structural template for the drug development targeting Enterococcus isolates.</p