De Novo Peptide Sequencing Reveals Many Cyclopeptides in the Human Gut and Other Environments

Bahar Behsaz; Hosein Mohimani; Alexey Gurevich; Andrey Prjibelski; Mark Fisher; Fernando Vargas; Larry Smarr; Pieter C Dorrestein; Joshua S Mylne; Pavel A Pevzner

doi:10.1016/j.cels.2019.11.007

De Novo Peptide Sequencing Reveals Many Cyclopeptides in the Human Gut and Other Environments

Cell Syst. 2020 Jan 22;10(1):99-108.e5. doi: 10.1016/j.cels.2019.11.007. Epub 2019 Dec 18.

Authors

Affiliations

¹ Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA. Electronic address: bbehsaz@ucsd.edu.
² Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA; Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.
³ Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
⁴ School of Molecular Sciences and the ARC Centre of Excellence in Plant Energy Biology, University of Western Australia, Crawley, WA, Australia.
⁵ Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
⁶ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA; California Institute for Telecommunications and Information Technology, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA.
⁷ Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California, San Diego, La Jolla, CA, USA.
⁸ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA; Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA.

PMID: 31864964
DOI: 10.1016/j.cels.2019.11.007

Abstract

Cyclic and branch cyclic peptides (cyclopeptides) represent a class of bioactive natural products that include many antibiotics and anti-tumor compounds. Despite the recent advances in metabolomics analysis, still little is known about the cyclopeptides in the human gut and their possible interactions due to a lack of computational analysis pipelines that are applicable to such compounds. Here, we introduce CycloNovo, an algorithm for automated de novo cyclopeptide analysis and sequencing that employs de Bruijn graphs, the workhorse of DNA sequencing algorithms, to identify cyclopeptides in spectral datasets. CycloNovo reconstructed 32 previously unreported cyclopeptides (to the best of our knowledge) in the human gut and reported over a hundred cyclopeptides in other environments represented by various spectra on Global Natural Products Social Molecular Network (GNPS). https://github.com/bbehsaz/cyclonovo.

Keywords: antimicrobial peptides; mass spectrometry; metabolomics; microbiome; natural products; peptide sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence / genetics*
Gastrointestinal Microbiome / genetics*
Humans
Mass Spectrometry
Peptides, Cyclic / chemistry*

Substances

Peptides, Cyclic

Abstract

Publication types

MeSH terms

Substances

Grants and funding