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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.

References

  1. Arnison, P. G. et al. Nat. Prod. Rep. 30, 108–160 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Müller, W. M., Schmiederer, T., Ensle, P. & Süssmuth, R. D. Angew. Chem. Int. Ed. Engl. 49, 2436–2440 (2010).

    Article  CAS  PubMed  Google Scholar 

  3. Hsu, S.-T. D. et al. Nat. Struct. Mol. Biol. 11, 963–967 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Caetano, T., Süssmuth, R. D. & Mendo, S. Curr. Microbiol. 70, 364–368 (2015).

    Article  CAS  PubMed  Google Scholar 

  5. Somma, S., Merati, W. & Parenti, F. Antimicrob. Agents Chemother. 11, 396–401 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meindl, K. et al. Angew. Chem. Int. Ed. Engl. 49, 1151–1154 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. May, M. Nature 509, S4–S5 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Krawczyk, J. M. et al. Chem. Biol. 20, 111–122 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Sit, C. S., Yoganathan, S. & Vederas, J. C. Acc. Chem. Res. 44, 261–268 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Kupke, T., Kempter, C., Jung, G. & Götz, F. J. Biol. Chem. 270, 11282–11289 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Steenbergen, J. N., Alder, J., Thorne, G. M. & Tally, F. P. J. Antimicrob. Chemother. 55, 283–288 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Kraas, F. I., Helmetag, V., Wittmann, M., Strieker, M. & Marahiel, M. A. Chem. Biol. 17, 872–880 (2010).

    Article  CAS  PubMed  Google Scholar 

  13. Li, J. & Jensen, S. E. Chem. Biol. 15, 118–127 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Süssmuth, R. D. & Mainz, A. Angew. Chem. Int. Ed. Engl. 56, 3770–3821 (2017).

    Article  CAS  PubMed  Google Scholar 

  15. Hong, H., Fill, T. & Leadlay, P. F. Angew. Chem. Int. Ed. Engl. 52, 13096–13099 (2013).

    Article  CAS  PubMed  Google Scholar 

  16. Etchegaray, A. & Machini, M. T. in Microbial Pathogens and Strategies for Combating Them: Science, Technology and Education. Vol. 2 (ed. Méndez-Vilas, A.) 951–959 (Formatex Research Center, 2013).

  17. Sardar, D., Lin, Z. & Schmidt, E. W. Chem. Biol. 22, 907–916 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jungmann, N. A., van Herwerden, E. F., Hügelland, M. & Süssmuth, R. D. ACS Chem. Biol. 11, 69–76 (2016).

    Article  CAS  PubMed  Google Scholar 

  19. Völler, G. H. et al. ChemBioChem 13, 1174–1183 (2012).

    Article  CAS  PubMed  Google Scholar 

  20. Wang, H. & van der Donk, W. A. ACS Chem. Biol. 7, 1529–1535 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cronan, J. E. & Thomas, J. Methods Enzymol. 459, 395–433 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hertweck, C., Luzhetskyy, A., Rebets, Y. & Bechthold, A. Nat. Prod. Rep. 24, 162–190 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Li, B. et al. Science 311, 1464–1467 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Hoshino, Y. et al. Int. J. Syst. Evol. Microbiol. 57, 1456–1460 (2007).

    Article  PubMed  Google Scholar 

  25. Gago, G., Diacovich, L., Arabolaza, A., Tsai, S.-C. & Gramajo, H. FEMS Microbiol. Rev. 35, 475–497 (2011).

    Article  CAS  PubMed  Google Scholar 

  26. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition. CLSI document M07-A10. (Wayne, PA, Clinical and Laboratory Standards Institute,2015).

  27. Weber, T. et al. Nucleic Acids Res. 43, W237–W243 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. States, D. J. & Gish, W. J. Comput. Biol. 1, 39–50 (1994).

    Article  CAS  PubMed  Google Scholar 

  29. Schwede, T., Kopp, J., Guex, N. & Peitsch, M. C. Nucleic Acids Res. 31, 3381–3385 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Florova, G., Kazanina, G. & Reynolds, K. A. Biochemistry 41, 10462–10471 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Gibson, D. G. et al. Nat. Methods 6, 343–345 (2009).

    Article  CAS  PubMed  Google Scholar 

  32. Andersen, K. R., Leksa, N. C. & Schwartz, T. U. Proteins Struct. Funct. Bioinforma. 81, 1857–1861 (2013).

    Article  CAS  Google Scholar 

  33. Majer, F., Schmid, D. G., Altena, K., Bierbaum, G. & Kupke, T. J. Bacteriol. 184, 1234–1243 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sievers, F. et al. Mol. Syst. Biol. 7, 539 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bachmann, B. O. & Ravel, J. Chapter 8. methods for in silico prediction of microbial polyketide and nonribosomal peptide biosynthetic pathways from DNA sequence data. Methods Enzymol. 458, 181–217 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

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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