Stress-Driven Discovery of New Angucycline-Type Antibiotics from a Marine NA-ZhouS1.

Natural products from marine actinomycetes remain an important resource for drug discovery, many of which are produced by the genus, Streptomyces. However, in standard laboratory conditions, specific gene clusters in microbes have long been considered silent or covert. Thus, various stress techniques activated latent gene clusters leading to isolation of potential metabolites. This study focused on the analysis of two new angucycline antibiotics isolated from the culture filtrate of a marine strain NA-ZhouS1, named, stremycin A () and B () which were further determined based on spectroscopic techniques such as high resolution time of flight mass spectrometry (HR-TOF-MS), 1D, and 2D nuclear magnetic resonance (NMR) experiments. In addition, four other known compounds, namely, 2-[2-(3,5-dimethyl-2-oxo-cyclohexyl)-6-oxo-tetrahydro-pyran-4yl]-acetamide (), cyclo[l-(4-hydroxyprolinyl)-l-leucine] (), 2-methyl-3-quinazoline-4-one (), and menthane derivative, 3-(hydroxymethyl)-6-isopropyl-10,12-dioxatricyclo[7.2.1.0]dodec-4-en-8-one () were obtained and elucidated by means of 1D NMR spectrometry. Herein, we describe the "Metal Stress Technique" applied in the discovery of angucyclines, a distinctive class of antibiotics that are commonly encoded in microbiomes but have never been reported in "Metal Stress" based discovery efforts. Novel antibiotics and exhibited antimicrobial activities against , methicillin resistant (MRSA), , and with equal minimum inhibitory concentration (MIC) values of 16 µg/mL, while these antibiotics showed inhibition against at MIC value of approximately 8⁻16 µg/mL, respectively. As a result, the outcome of this investigation revealed that metal stress is an effective technique in unlocking the biosynthetic potential and resulting production of novel antibiotics.