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Sublancin is not a lantibiotic but an S-linked glycopeptide

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Abstract

Sublancin is shown to be an S-linked glycopeptide containing a glucose attached to a cysteine residue, establishing a new post-translational modification. The activity of the S-glycosyl transferase was reconstituted in vitro, and the enzyme is shown to have relaxed substrate specificity, allowing the preparation of analogs of sublancin. Glycosylation is essential for its antimicrobial activity.

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Figure 1: Analysis of the structure of sublancin by tandem mass spectrometry.
Figure 2: In vitro reconstitution of SunS activity and sublancin antimicrobial activity.

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Acknowledgements

This work was supported by the US National Institutes of Health (GM58822 to W.A.v.d.D.) and a US National Institutes of Health Cellular and Molecular Biology Training Grant (T32 GM007283 to T.J.O.). X.N.O. was supported by the EXROP summer research program of the Howard Hughes Medical Institute.

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Contributions

T.J.O. performed mass spectrometric analyses and all biochemical assays shown, which were designed and analyzed by T.J.O. and W.A.v.d.D. J.M.B. performed NMR analysis. H.W. prepared and performed biochemical assays of the SunA mutant peptides. X.N.O. assisted with purification of sublancin and mass spectrometric analyses. T.J.O. and W.A.v.d.D. wrote the manuscript.

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Correspondence to Wilfred A van der Donk.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Figures 1–21 and Supplementary Table 1 (PDF 8959 kb)

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Oman, T., Boettcher, J., Wang, H. et al. Sublancin is not a lantibiotic but an S-linked glycopeptide. Nat Chem Biol 7, 78–80 (2011). https://doi.org/10.1038/nchembio.509

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