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CYCLONE—A Utility for De Novo Sequencing of Microbial Cyclic Peptides

  • Focus: MS in the Characterization of Microorganisms: Research Article
  • Published:
Journal of The American Society for Mass Spectrometry

Abstract

We have developed a de novo sequencing software tool (CYCLONE) and applied it for determination of cyclic peptides. The program uses a non-redundant database of 312 nonribosomal building blocks identified to date in bacteria and fungi (more than 230 additional residues in the database list were isobaric). The software was used to fully characterize the tandem mass spectrum of several cyclic peptides and provide sequence tags. The general strategy of the script was based on fragment ion pre-characterization to accomplish unambiguous b-ion series assignments. Showcase examples were a cyclic tetradepsipeptide beauverolide, a cyclic hexadepsipeptide roseotoxin A, a lasso-like hexapeptide pseudacyclin A, and a cyclic undecapeptide cyclosporin A. The extent of ion scrambling in smaller peptides was as low as 5 % of total ion current; this demonstrated the feasibility of CYCLONE de novo sequencing. The robustness of the script was also tested against database sets of various sizes and isotope-containing data. It can be downloaded from the http://ms.biomed.cas.cz/MSTools/ website.

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Acknowledgments

The authors acknowledge support for this work from the Ministry of Education, Youth, and Sports of the Czech Republic (ME10013), IMIC institutional research concept RVO61388971, Charles University in Prague (UNCE_204025/2012), and Czech Science Foundation (P206/12/1150).

The authors thank their colleague Petr Man for helpful discussion in the initial stage of script preparation.

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Authors and Affiliations

  1. Institute of Microbiology, v.v.i., Videnska 1083, CZ 14220, Prague 4, Czech Republic

    Daniel Kavan, Marek Kuzma, Karel Lemr & Vladimir Havlicek

  2. Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, 127 40, Prague 2, Czech Republic

    Daniel Kavan

  3. Department of Analytical Chemistry, Faculty of Science, Palacky University, Department of Analytical Chemistry, RCPTM, 17. listopadu 12, 771 46, Olomouc, Czech Republic

    Karel Lemr & Vladimir Havlicek

  4. Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, 76019-0065, USA

    Kevin A. Schug

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  1. Daniel Kavan
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  2. Marek Kuzma
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  5. Vladimir Havlicek
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Correspondence to Vladimir Havlicek.

Additional information

This paper is dedicated to our colleague and friend professor Catherine Fenselau in recognition of the 2012 ASMS Award for Distinguished Contribution in Mass Spectrometry.

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This material is available free of charge via the Internet at: http://www.springerlink.com/content/1044-0305?MUD=MP

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Kavan, D., Kuzma, M., Lemr, K. et al. CYCLONE—A Utility for De Novo Sequencing of Microbial Cyclic Peptides. J. Am. Soc. Mass Spectrom. 24, 1177–1184 (2013). https://doi.org/10.1007/s13361-013-0652-7

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  • DOI: https://doi.org/10.1007/s13361-013-0652-7

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