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The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine

Abstract

Albicidin is a potent DNA gyrase inhibitor produced by the sugarcane pathogenic bacterium Xanthomonas albilineans. Here we report the elucidation of the hitherto unknown structure of albicidin, revealing a unique polyaromatic oligopeptide mainly composed of p-aminobenzoic acids. In vitro studies provide further insights into the biosynthetic machinery of albicidin. These findings will enable structural investigations on the inhibition mechanism of albicidin and its assessment as a highly effective antibacterial drug.

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Figure 1: Structural characterization of albicidin.
Figure 2: Model of albicidin biosynthesis.

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Acknowledgements

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG SU239/11-1; SU 18-1), by the Cluster of Excellence 'Unifying Concepts in Catalysis (UniCat)' (DFG) and by a grant from the Agence Nationale de la Recherche (ANR-09-BLAN-0413-01).

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Authors

Contributions

S.C., A.P., S.D., M.M., J.N., I.P., M.H., P.R. and M.R. performed the cultivation and isolation of albicidin. A.P., D.P., V.S., S.K. and A.M. performed the structural elucidation of albicidin. D.P., S.U., A.M. and M.R. performed the bioinformatic analysis of the biosynthesis genes. D.P., S.U. and M.H. produced the proteins and performed the in vitro assays. J.K. synthetized the substrates for the in vitro assay. S.C., A.P., D.P., A.M., M.R. and R.D.S. designed the study and analyzed the data. S.C., A.P., D.P., L.V., A.M., M.R. and R.D.S. wrote the manuscript.

Corresponding authors

Correspondence to Monique Royer or Roderich D Süssmuth.

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The authors declare no competing financial interests.

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Supplementary Results, Supplementary Tables 1–6 and Supplementary Figures 1–12. (PDF 2134 kb)

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Cociancich, S., Pesic, A., Petras, D. et al. The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine. Nat Chem Biol 11, 195–197 (2015). https://doi.org/10.1038/nchembio.1734

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  • DOI: https://doi.org/10.1038/nchembio.1734

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