Annotating and Interpreting Linear and Cyclic Peptide Tandem Mass Spectra

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1401)

Abstract

Nonribosomal peptides often possess pronounced bioactivity, and thus, they are often interesting hit compounds in natural product-based drug discovery programs. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and, especially in the case of cyclic peptides, the complex fragmentation patterns observed. This makes nonribosomal peptide tandem mass spectra annotation challenging and time-consuming. To meet this challenge, software tools for this task have been developed. In this chapter, the workflow for using the software mMass for the annotation of experimentally obtained peptide tandem mass spectra is described. mMass is freely available (http://www.mmass.org), open-source, and the most advanced and user-friendly software tool for this purpose. The software enables the analyst to concisely annotate and interpret tandem mass spectra of linear and cyclic peptides. Thus, it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides.

Key words

Nonribosomal peptides Tandem mass spectrometry In silico fragmentation Annotation Linear peptides Cyclic peptides Depsipeptides 

Notes

Acknowledgment

The author thanks R. Pozzi, T. Schafhauser and M. Strohalm for critically reading the manuscript and suggesting improvements.

References

  1. 1.
    Tiburzi F, Visca P, Imperi F (2007) Do nonribosomal peptide synthetases occur in higher eukaryotes? IUBMB Life 59:730–733CrossRefPubMedGoogle Scholar
  2. 2.
    Caboche S, Leclère V, Pupin M, Kucherov G et al (2010) Diversity of monomers in nonribosomal peptides: towards the prediction of origin and biological activity. J Bacteriol 192:5143–5150PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Tidgewell K, Clark BR, Gerwick WH (2010) The natural products chemistry of cyanobacteria. In: Mander L, Liu H-W (eds) Comprehensive natural products II: chemistry and biology. Elsevier, Oxford, pp 141–188CrossRefGoogle Scholar
  4. 4.
    Niedermeyer T, Brönstrup M (2012) Natural-product drug discovery from microalgae. In: Posten C, Walter C (eds) Microalgal biotechnology: integration and economy. de Gruyter, Berlin, pp 169–200Google Scholar
  5. 5.
    Ziemert N, Ishida K, Liaimer A, Hertweck C et al (2008) Ribosomal synthesis of tricyclic depsipeptides in bloom-forming cyanobacteria. Angew Chemie Int Ed 47:7756–7759CrossRefGoogle Scholar
  6. 6.
    Velásquez JE, van der Donk WA (2011) Genome mining for ribosomally synthesized natural products. Curr Opin Chem Biol 15:11–21PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Marahiel MA (2009) Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis. J Pept Sci 15: 799–807CrossRefPubMedGoogle Scholar
  8. 8.
    Schwarzer D, Finking R, Marahiel MA (2003) Nonribosomal peptides: from genes to products. Nat Prod Rep 20:275–287CrossRefPubMedGoogle Scholar
  9. 9.
    Strieker M, Tanović A, Marahiel MA (2010) Nonribosomal peptide synthetases: structures and dynamics. Curr Opin Struct Biol 20: 234–240CrossRefPubMedGoogle Scholar
  10. 10.
    Finking R, Marahiel MA (2004) Biosynthesis of nonribosomal peptides. Annu Rev Microbiol 58:453–488CrossRefPubMedGoogle Scholar
  11. 11.
    Tillett D, Dittmann E, Erhard M, von Döhren H et al (2000) Structural organization of microcystin biosynthesis in Microcystis aeruginosa PCC7806: an integrated peptide-polyketide synthetase system. Chem Biol 7: 753–764CrossRefPubMedGoogle Scholar
  12. 12.
    Dittmann E, Neilan BA, Börner T (2001) Molecular biology of peptide and polyketide biosynthesis in cyanobacteria. Appl Microbiol Biotechnol 57:467–473CrossRefPubMedGoogle Scholar
  13. 13.
    Christiansen G, Fastner J, Erhard M, Börner T et al (2003) Microcystin biosynthesis in planktothrix: genes, evolution, and manipulation. J Bacteriol 185:564–572PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Caboche S, Pupin M, Leclère V et al (2008) NORINE: a database of nonribosomal peptides. Nucleic Acids Res 36:326–331CrossRefGoogle Scholar
  15. 15.
    Dreyfuss M, Härri E, Hofmann H et al (1976) Cyclosporin A and C: new metabolites from Trichoderma polysporum. Microbiology 133: 125–133Google Scholar
  16. 16.
    Von Wartburg A, Traber R (1988) Cyclosporins, fungal metabolites with immunosuppressive activities. Prog Med Chem 25: 1–33Google Scholar
  17. 17.
    McCormick MH, Stark WM, Pittenger GE et al (1956) Vancomycin, a new antibiotic. I. Chemical and biologic properties. Antibiot Annu 3:606–611Google Scholar
  18. 18.
    Nagarajan R (1991) Antibacterial activities and modes of action of vancomycin and related glycopeptides. Antimicrob Agents Chemother 35:605–609PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Rohr J (2006) Cryptophycin anticancer drugs revisited. ACS Chem Biol 1:747–750CrossRefPubMedGoogle Scholar
  20. 20.
    Rusconi F (2009) massXpert 2: a cross-platform software environment for polymer chemistry modelling and simulation/analysis of mass spectrometric data. Bioinformatics 25:2741–2742CrossRefPubMedGoogle Scholar
  21. 21.
    Jagannath S, Sabareesh V (2007) Peptide Fragment Ion Analyser (PFIA): a simple and versatile tool for the interpretation of tandem mass spectrometric data and de novo sequencing of peptides. Rapid Commun Mass Spectrom 21:3033–3038CrossRefPubMedGoogle Scholar
  22. 22.
    Liu W, Ng J, Meluzzi D, Bandeira N et al (2009) The interpretation of tandem mass spectra obtained from cyclic non-ribosomal peptides. Anal Chem 81:4200–4209PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Niedermeyer THJ, Strohalm M (2012) mMass as a software tool for the annotation of cyclic peptide tandem mass spectra. PLoS One 7:e44913PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Interfaculty Institute for Microbiology and Infection MedicineEberhard Karls UniversityTübingenGermany
  2. 2.German Centre for Infection Research (DZIF)TübingenGermany

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