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.
Similar content being viewed by others
References
Sieber, S.A. & Marahiel, M.A. Chem. Rev. 105, 715–738 (2005).
Newman, D.J. & Cragg, G.M. J. Nat. Prod. 70, 461–477 (2007).
Hamada, T., Matsunaga, S., Yano, G. & Fusetani, N. J. Am. Chem. Soc. 127, 110–118 (2005).
Ireland, C.M., Durso, A.R., Newman, R.A. & Hacker, M.P. J. Org. Chem. 47, 360–361 (1982).
Li, J., Burgett, A., Esser, L., Amezcua, C. & Harran, P. Angew. Chem. Int. Edn Engl. 40, 4770–4773 (2001).
Lang, G. et al. J. Nat. Prod. 71, 1595–1599 (2008).
Krishnamurthy, T. et al. Proc. Natl. Acad. Sci. USA 86, 770–774 (1989).
Gerwick, W.H., Jiang, Z.D., Agarwal, S.K. & Farmer, B.T. Tetrahedron 48, 2313–2324 (1992).
Barber, M. et al. Int. J. Mass Spectrom. Ion Process. 122, 143–151 (1992).
Hitzeroth, G., Vater, J., Franke, P., Gebhardt, K. & Fiedler, H.P. Rapid Commun. Mass Spectrom. 19, 2935–2942 (2005).
Welker, M., Marsálek, B., Sejnohová, L. & von Döhren, H. Peptides 27, 2090–2103 (2006).
Caboche, S. et al. Nucleic Acids Res. 36, D326–D331 (2008).
Skiena, S.S. & Sundaram, G. Bull. Math. Biol. 56, 275–294 (1994).
Rosenblatt, J. & Seymour, P.D. SIAM Journal on Algebraic and Discrete Methods 3, 343–350 (1982).
Pevzner, P.A., Dancik, V. & Tang, C. J. Comput. Biol. 7, 777–787 (2000).
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.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–4, Supplementary Tables 1–3 and Supplementary Notes 1–2 (PDF 676 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmeth.1350
- Springer Nature America, Inc.
This article is cited by
-
Discovery and biosynthesis of cyclic plant peptides via autocatalytic cyclases
Nature Chemical Biology (2022)
-
Toward a global picture of bacterial secondary metabolism
Journal of Industrial Microbiology and Biotechnology (2019)
-
Increased diversity of peptidic natural products revealed by modification-tolerant database search of mass spectra
Nature Microbiology (2018)
-
A strategy for the identification of patterns in the biosynthesis of nonribosomal peptides by Betaproteobacteria species
Scientific Reports (2017)
-
Dereplication of peptidic natural products through database search of mass spectra
Nature Chemical Biology (2017)