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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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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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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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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DOI: https://doi.org/10.1038/s41589-018-0068-6
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