Identification of novel endophenaside antibiotics produced by Kitasatospora sp. MBT66

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Abstract

Actinomycetes are a major source of bioactive secondary metabolites and are a focal point in the search for novel antimicrobial compounds that are needed to combat multidrug-resistant pathogens. Here, we report the discovery of several novel phenazine-type antibiotics produced by Kitasatospora sp. MBT66. These include the novel glycosylated endophenazines A–E (15), together with N-prenylated endophenazine F1 (6). Compounds 1 and 3 contain a 2′-O-methylation of the sugar moiety, which is rare in nature and reported for the first time in connection with phenazines. The structures of the new compounds were determined on the basis of their spectral data, including 1D and 2D NMR, HR-MS and the gene cluster responsible for the biosynthesis of phenazines was identified. All phenazine derivatives showed antimicrobial activity against the Gram-positive Bacillus subtilis, while compounds 1–3 and 5 also inhibited growth of the Gram-negative Escherichia coli.

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Acknowledgements

The work was supported by a PhD Fellowship from the China Scholarship Council to CSW, and by grants from the Netherlands Technology Foundation (10467 and 11992) to GPvW. Physics data of compounds 16, Structure elucidation of compounds 24 and 6, instability of compound 5 in methanol, detection of endophenazines, as well as HRESIMS, IR, UV, 1D and 2D NMR spectra of compounds 16 are available.

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Correspondence to Gilles P van Wezel.

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Wu, C., van Wezel, G. & Hae Choi, Y. Identification of novel endophenaside antibiotics produced by Kitasatospora sp. MBT66. J Antibiot 68, 445–452 (2015) doi:10.1038/ja.2015.14

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