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Mar. Drugs 2018, 16(9), 331; https://doi.org/10.3390/md16090331

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

1
Ocean College, Zhejiang University, Hangzhou 310058, China
2
Department of Chemistry, Zhejiang University, Hangzhou 301000, China
3
Department of Chemistry, Zhejiang Gongshang University, Hangzhou 310012, China
4
Key Laboratory of Applied Marine Biotechnology, Ningbo University, Chinese Ministry of Education, Ningbo 315211, China
5
Centre of Analysis and Measurement, Zhejiang University, Hangzhou 310058, China
*
Author to whom correspondence should be addressed.
Received: 20 July 2018 / Revised: 31 August 2018 / Accepted: 7 September 2018 / Published: 12 September 2018
(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)
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Abstract

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 Streptomyces pratensis strain NA-ZhouS1, named, stremycin A (1) and B (2) 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 (3), cyclo[l-(4-hydroxyprolinyl)-l-leucine] (4), 2-methyl-3H-quinazoline-4-one (5), and menthane derivative, 3-(hydroxymethyl)-6-isopropyl-10,12-dioxatricyclo[7.2.1.0]dodec-4-en-8-one (6) 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 1 and 2 exhibited antimicrobial activities against Pseudomonas aeruginosa, methicillin resistant Staphylococcus aureus (MRSA), Klebsiella pneumonia, and Escherichia coli with equal minimum inhibitory concentration (MIC) values of 16 µg/mL, while these antibiotics showed inhibition against Bacillus subtilis 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. View Full-Text
Keywords: marine microorganisms; Streptomyces pratensis; polyketide antibiotics; metal stress technique; antimicrobial activity marine microorganisms; Streptomyces pratensis; polyketide antibiotics; metal stress technique; antimicrobial activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Akhter, N.; Liu, Y.; Auckloo, B.N.; Shi, Y.; Wang, K.; Chen, J.; Wu, X.; Wu, B. Stress-Driven Discovery of New Angucycline-Type Antibiotics from a Marine Streptomyces pratensis NA-ZhouS1. Mar. Drugs 2018, 16, 331.

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