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Dereplication and de novo sequencing of nonribosomal peptides

Abstract

Nonribosomal peptides (NRPs) are of great pharmacological importance, but there is currently no technology for high-throughput NRP 'dereplication' and sequencing. We used multistage mass spectrometry followed by spectral alignment algorithms for sequencing of cyclic NRPs. We also developed an algorithm for comparative NRP dereplication that establishes similarities between newly isolated and previously identified similar but nonidentical NRPs, substantially reducing dereplication efforts.

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Figure 1: Experimental and theoretical spectra of seglitide.

References

  1. Sieber, S.A. & Marahiel, M.A. Chem. Rev. 105, 715–738 (2005).

    Article  CAS  Google Scholar 

  2. Newman, D.J. & Cragg, G.M. J. Nat. Prod. 70, 461–477 (2007).

    Article  CAS  Google Scholar 

  3. Hamada, T., Matsunaga, S., Yano, G. & Fusetani, N. J. Am. Chem. Soc. 127, 110–118 (2005).

    Article  CAS  Google Scholar 

  4. Ireland, C.M., Durso, A.R., Newman, R.A. & Hacker, M.P. J. Org. Chem. 47, 360–361 (1982).

    Article  Google Scholar 

  5. Li, J., Burgett, A., Esser, L., Amezcua, C. & Harran, P. Angew. Chem. Int. Edn Engl. 40, 4770–4773 (2001).

    Article  CAS  Google Scholar 

  6. Lang, G. et al. J. Nat. Prod. 71, 1595–1599 (2008).

    Article  CAS  Google Scholar 

  7. Krishnamurthy, T. et al. Proc. Natl. Acad. Sci. USA 86, 770–774 (1989).

    Article  CAS  Google Scholar 

  8. Gerwick, W.H., Jiang, Z.D., Agarwal, S.K. & Farmer, B.T. Tetrahedron 48, 2313–2324 (1992).

    Article  CAS  Google Scholar 

  9. Barber, M. et al. Int. J. Mass Spectrom. Ion Process. 122, 143–151 (1992).

    Article  CAS  Google Scholar 

  10. Hitzeroth, G., Vater, J., Franke, P., Gebhardt, K. & Fiedler, H.P. Rapid Commun. Mass Spectrom. 19, 2935–2942 (2005).

    Article  CAS  Google Scholar 

  11. Welker, M., Marsálek, B., Sejnohová, L. & von Döhren, H. Peptides 27, 2090–2103 (2006).

    Article  CAS  Google Scholar 

  12. Caboche, S. et al. Nucleic Acids Res. 36, D326–D331 (2008).

    Article  CAS  Google Scholar 

  13. Skiena, S.S. & Sundaram, G. Bull. Math. Biol. 56, 275–294 (1994).

    Article  CAS  Google Scholar 

  14. Rosenblatt, J. & Seymour, P.D. SIAM Journal on Algebraic and Discrete Methods 3, 343–350 (1982).

    Article  Google Scholar 

  15. Pevzner, P.A., Dancik, V. & Tang, C. J. Comput. Biol. 7, 777–787 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank G. Kucherov for many helpful discussions and members of the Norine team for helping with the Norine database; D. Meluzzi for the help in the data collection process; B. Moore (Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego) and A. Schultz (Scripps Institution of Oceanography, University of California, San Diego) for providing the cyclomarin compounds, and W. Fenical (Scripps Institution of Oceanography, University of California, San Diego) and K. Maloney (Scripps Institution of Oceanography, University of California, San Diego) for providing compound 879. This project was supported by US National Institutes of Health grants 1-P41-RR024851-01, GM086283 and cA10u851, and by the PhRMA foundation.

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Correspondence to Pavel A Pevzner.

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Supplementary Figures 1–4, Supplementary Tables 1–3 and Supplementary Notes 1–2 (PDF 676 kb)

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Ng, J., Bandeira, N., Liu, WT. et al. Dereplication and de novo sequencing of nonribosomal peptides. Nat Methods 6, 596–599 (2009). https://doi.org/10.1038/nmeth.1350

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