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The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides

Nature Chemical Biology volume 14, pages 652–654 (2018)Cite this article

Abstract

The potent antibacterial lanthipeptide microvionin, isolated from a culture of Microbacterium arborescens, exhibits a new triamino-dicarboxylic acid moiety, termed avionin, and an unprecedented N-terminal guanidino fatty acid. We identified the corresponding biosynthetic gene cluster and reconstituted central steps of avionin biosynthesis in vitro. Genome mining and isolation of nocavionin from Nocardia terpenica revealed a widespread distribution of this lanthipeptide class, termed lipolanthines, which may be useful as future antimicrobial drugs.

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Fig. 1: Structure and biosynthetic gene cluster of microvionin.
Fig. 2: MicKC- and MicD-mediated formation of the avionin moiety in vitro.
Fig. 3: Genome mining for lipolanthines.

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Acknowledgements

This research was supported by grants of the Deutsche Forschungsgemeinschaft (Project No.: SU 239/25-1). We thank L. Steinhäuser and R. Al Toma for helpful discussions and advice.

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Authors and Affiliations

  1. Faculty II – Department of Chemistry, Technische Universität Berlin, Berlin, Germany

    Vincent Wiebach, Andi Mainz, Mary-Ann J. Siegert, Natalia A. Jungmann & Roderich D. Süssmuth

  2. Deinobiotics, Grabels, France

    Guillaume Lesquame, Assia Dreux-Zigha, Jozsef Aszodi & Dominique Le Beller

  3. ICV-Institute Charles Viollette, Univ. Lille, INRA, ISA, Univ. Artois, Univ. Littoral Côte d’Opale, Lille, France

    Sophie Tirat

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  1. Vincent Wiebach
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Contributions

V.W. cloned the expression vectors, performed the genome mining, set up the in vitro assays and conducted the MS and tandem MS measurements. A.M. performed the NMR experiments and the subsequent NMR structure elucidation. M.-A.J.S. synthesized the synthetic precursor peptide. N.A.J. identified and annotated the microvionin gene cluster from the genomic data. G.L., S.T. and A.D.-Z. conducted the screening experiments, isolated microvionin and nocavionin and determined MICs. J.A., D.L.B., A.M. and R.D.S. designed the experiments. V.W., A.M. and R.D.S. wrote the paper.

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Correspondence to Roderich D. Süssmuth.

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Supplementary Figures 1–17, Supplementary Tables 1–7, Supplementary Notes 1–2

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Wiebach, V., Mainz, A., Siegert, MA.J. et al. The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides. Nat Chem Biol 14, 652–654 (2018). https://doi.org/10.1038/s41589-018-0068-6

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