Advertisement

De Novo Sequencing of Nonribosomal Peptides

  • Nuno Bandeira
  • Julio Ng
  • Dario Meluzzi
  • Roger G. Linington
  • Pieter Dorrestein
  • Pavel A. Pevzner
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4955)

Abstract

While nonribosomal peptides (NRPs) are of tremendous pharmacological importance, there is currently no technology capable of high-throughput sequencing of NRPs. Difficulties in sequencing NRPs slow down the progress in elucidating the non-ribosomal genetic code and negatively affect various screening programs aimed at the discovery of natural compounds of medical importance. We propose to employ multi-stage mass-spectrometry (MS n ) for the data acquisition, followed by alignment-based heuristic algorithms for data analysis. Since mass spectrometry based analysis of NRPs is fast and inexpensive, this approach opens the possibility of high-throughput sequencing of many unknown NRPs accumulated in large screening programs.

Keywords

Cyclic Peptides Sequencing De novo Algorithm 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sieber, S.A., Marahiel, M.A.: Molecular Mechanisms Underlying Nonribosomal Peptide Synthesis: Approaches to New Antibiotics. Chem. Rev. 105, 715–738 (2005)CrossRefGoogle Scholar
  2. 2.
    Dorrestein, P.C., Kelleher, N.L.: Dissecting Non-ribosomal and Polyketide Biosynthetic Machineries Using Electrospray Ionization Fourier-Transform Mass Spectrometry. Natural Product Reports 23, 893–918 (2006)CrossRefGoogle Scholar
  3. 3.
    Welker, M., Von Doehren, H.: Cyanobacterial Peptides - Nature’s Own Combinatorial Biosynthesis. FEMS Microbiology Reviews 30, 530–563 (2006)CrossRefGoogle Scholar
  4. 4.
    Butcher, B.G., Helmann, J.D.: Identification of Bacillus subtilis Sigma-dependent Genes that Provide Intrinsic Resistance to Antimicrobial Compounds Produced by Bacilli. Mol. Microbiol. 60, 765–782 (2006)CrossRefGoogle Scholar
  5. 5.
    Williams, D., Austin, P., Diaz-Marrero, A., Soest, R., Matainaho, T., Roskelley, C., Roberge, M., Andersen, R.: Neopetrosiamides, Peptides from the Marine Sponge Neopetrosia sp. That Inhibit Amoeboid Invasion by Human Tumor Cells. Organic Letters 7, 4173–4176 (2005)CrossRefGoogle Scholar
  6. 6.
    Luesch, H., Williams, P., Yoshida, W., Moore, R., Paul, V.: Ulongamides A-F, New Beta-Amino Acid-Containing Cyclodepsipeptides from Palauan Collections of the Marine Cyanobacterium Lyngbya sp. Journal of Natural Products 65, 996–1000 (2002)CrossRefGoogle Scholar
  7. 7.
    Hamada, T., Matsunaga, S., Yano, G., G nd Fusetani, N.: Polytheonamides A and B, Highly Cytotoxic, Linear Polypeptides with Unprecedented Structural Features, from the Marine Sponge, Theonella swinhoei. J Am. Chem. Soc. 127, 110–118 (2005)CrossRefGoogle Scholar
  8. 8.
    Ireland, C.M., Durso, A.R., Newman, R.A., Hacker, M.P.: Antineoplastic Cyclic Peptides from the Marine Tunicate Lissoclinum patella. J. Org. Chem. 47, 360–361 (1982)CrossRefGoogle Scholar
  9. 9.
    Kurosawa, K., Matsuura, K., Chida, N.: Total Synthesis of Stevastelins B3 and C3: Structure Confirmation of Stevastelin B3 and Revision of Stevastelin C3. Tetrahedron Letters 46, 389–392 (2005)CrossRefGoogle Scholar
  10. 10.
    Li, J., Burgett, A., Esser, L., Amezcua, C., G.Harran, P.: Total synthesis of nominal diazonamides: Part 2. on the true structure and origin of natural isolates. Angew. Chem Intl. Ed. Engl., 4771–4773 (2001)Google Scholar
  11. 11.
    Ikeda, H., Nonomiya, T., Ōmura, S.: Organization of Biosynthetic Gene Cluster for Avermectin in Streptomyces avermitilis: Analysis of Enzymatic Domains in Four Polyketide Synthases. Journal of Industrial Microbiology and Biotechnology 27, 170–176 (2001)CrossRefGoogle Scholar
  12. 12.
    Watanabe, K., Hotta, K., Praseuth, A.P., Koketsu, K., Migita, A., Boddy, C.N., Wang, C.C., Oguri, H., Oikawa, H.: Total Biosynthesis of Antitumor Nonribosomal Peptides in Escherichia coli. Nat. Chem. Biol. 2, 423–428 (2006)CrossRefGoogle Scholar
  13. 13.
    Barber, M., Bell, D.J., Morris, M.R., Tetler, L.W., Monaghan, J.J., Morden, W.E., Bycroft, B.W., Green, B.N.: An Investigation of the Tyrothricin Complex by Tandem Mass Spectrometry. International Journal of Mass Spectrometry and Ion Processes 122, 143–151 (1992)CrossRefGoogle Scholar
  14. 14.
    Hitzeroth, G., Vater, J., Franke, P., Gebhardt, K., Fiedler, H.P.: Whole Cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and in situ Structure Analysis of Streptocidins, a Family of Tyrocidine-like Cyclic Peptides. Rapid Communications in Mass Spectrometry 19, 2935–2942 (2005)CrossRefGoogle Scholar
  15. 15.
    Gebhardt, K., Pukall, R., Fiedler, H.P.: Streptocidins A-D, Novel Cyclic Decapeptide Antibiotics Produced by Streptomyces sp. Tü 6071. I. Taxonomy, Fermentation, Isolation and Biological Activities. Antibiot. 54, 428–433 (2001)Google Scholar
  16. 16.
    Höltzel, A., Jack, R.W., Nicholson, G.J., Jung, G., Gebhardt, K., Fiedler, H.P., Süssmuth, R.D.: Streptocidins A-D, Novel Cyclic Decapeptide Antibiotics Produced by Streptomyces sp. Tü 6071. II. Structure elucidation. Antibiot. 54, 434–440 (2005)Google Scholar
  17. 17.
    Redman, J., Wilcoxen, K., Ghadiri, M.: Automated Mass Spectrometric Sequence Determination of Cyclic Peptide Library Members. Journal of Combinatorial Chemistry 5, 33–40 (2003)CrossRefGoogle Scholar
  18. 18.
    Olsen, J.V., Mann, M.: Improved Peptide Identification in Proteomics by Two Consecutive Stages of Mass Spectrometric Fragmentation. Proc. Natl. Acad. Sci. 101, 13417–13422 (2004)CrossRefGoogle Scholar
  19. 19.
    Ulintz, P.J., Bodenmiller, B., Andrews, P.C., Aebersold, R., Nesvizhskii, A.I.: Investigating MS2-MS3 Matching Statistics: A Model for Coupling Consecutive Stage Mass Spectrometry Data for Increased Peptide Identification Confidence. In: Molecular Cellular Proteomics, pp. M700128–MCP200 (2007)Google Scholar
  20. 20.
    Skiena, S.S., Sundaram, G.: A Partial Digest Approach to Restriction Site Mapping. Bulletin of Mathematical Biology 56, 275–294 (1994)zbMATHGoogle Scholar
  21. 21.
    Rosenblatt, J., Seymour, P.D.: The Structure of Homometric Sets. SIAM Journal on Algebraic and Discrete Methods 3, 343–350 (1982)CrossRefMathSciNetzbMATHGoogle Scholar
  22. 22.
    Cieliebak, M., Eidenbenz, S., Penna, P.: Partial Digest Problem is Hard to Solve for Erroneous Input Data. Theoretical Computer Science 349, 361–381 (2005)MathSciNetzbMATHGoogle Scholar
  23. 23.
    Xu, C., Ma, B.: Complexity and Scoring Function of MS/MS Peptide De Novo Sequencing. Computational Systems Bioinformatics 5, 361–369 (2006)Google Scholar
  24. 24.
    Pevzner, P.A., Dancik, V., Tang, C.: Mutation-Tolerant Protein Identification by Mass Spectrometry. J Comput. Biol. 7, 777–787 (2000)CrossRefGoogle Scholar
  25. 25.
    Bandeira, N., Clauser, K.R., Pevzner, P.A.: Shotgun Protein Sequencing: Assembly of Peptide Tandem Mass Spectra from Mixtures of Modified Proteins. Mol. Cell Proteomics 6, 1123–1134 (2007)CrossRefGoogle Scholar
  26. 26.
    Bandeira, N., Tsur, D., Frank, A., Pevzner, P.A.: Protein Identification by Spectral Networks Analysis. Proceedings of the National Academy of Sciences 104, 6140–6145 (2007)CrossRefGoogle Scholar
  27. 27.
    Bern, M., Goldberg, D.: De Novo Analysis of Peptide Tandem Mass Spectra by Spectral Graph Partitioning. Journal of Computational Biology 13, 364–378 (2006)CrossRefMathSciNetGoogle Scholar
  28. 28.
    Chen, T., Kao, M.Y., Tepel, M., Rush, J., Church, G.M.: A Dynamic Programming Approach to De Novo Peptide Sequencing via Tandem Mass Spectrometry. J Comput. Biol. 8, 325–337 (2001)CrossRefGoogle Scholar
  29. 29.
    B’Hymer, C., Montes-Bayon, M., Caruso, J.A.: Marfey’s Reagent: Past, Present, and Future Uses of 1-Fluoro-2,4-Dinitrophenyl-5-L-Alanine Amide. Journal of Separation Science 26, 7–19 (2003)CrossRefGoogle Scholar
  30. 30.
    Bandeira, N., Tang, H., Bafna, V., Pevzner, P.: Shotgun Protein Sequencing by Tandem Mass Spectra Assembly. Analytical Chemistry 76, 7221–7233 (2004)CrossRefGoogle Scholar
  31. 31.
    Dancik, V., Addona, T., Clauser, K., Vath, J., Pevzner, P.: De Novo Peptide Sequencing via Tandem Mass Spectrometry. J Comput. Biol. 6, 327–342 (1999)CrossRefGoogle Scholar
  32. 32.
    Frank, A.M., Pevzner, P.A.: PepNovo: De Novo Peptide Sequencing via Probabilistic Network Modeling. Anal. Chem. 77, 964–973 (2005)CrossRefGoogle Scholar
  33. 33.
    Mo, L., Dutta, D., Wan, Y., Chen, T.: MSNovo: A Dynamic Programming Algorithm for De Novo Peptide Sequencing via Tandem Mass Spectrometry. Anal. Chem. 79, 4870–4878 (2007)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Nuno Bandeira
    • 1
  • Julio Ng
    • 1
  • Dario Meluzzi
    • 1
  • Roger G. Linington
    • 2
  • Pieter Dorrestein
    • 1
  • Pavel A. Pevzner
    • 1
  1. 1.University of CaliforniaSan DiegoUSA
  2. 2.University of CaliforniaSanta CruzUSA

Personalised recommendations