Deletion of the accramycin pathway-specific regulatory gene activates the production of unrelated polyketide metabolites.

The manipulation of regulatory genes has been employed to awaken cryptic metabolites in . 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, in 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-4-pyran-4-one (), zanthopyranone (), propioveratrone (), and TW94a (). To the best of our knowledge, this is the first report of the isolation of from bacteria. Compounds , , and showed weak to moderate activity against , , and . Propioveratrone () displayed better inhibitory activity (MIC = 6.3 μg/mL) than ampicillin against multi-drug resistant K6039 clinical isolate (MIC = 25 μg/mL), suggesting a promising structural template for the drug development targeting isolates.