De Novo Peptide Sequencing Reveals a Vast Cyclopeptidome in Human Gut and Other Environments

preprint · bioRxiv · 2019

preprint · bioRxiv · 2019. Bahar Behsaz et al. Cyclic and branch cyclic peptides (cyclopeptides) represent an important class of bioactive natural products…
Date 2019-01-16
Type preprint
Venue bioRxiv
Publisher openRxiv
Contribution algorithm
DOI 10.1101/521872
Citations (OpenAlex) 0

Peer-reviewed version: De Novo Peptide Sequencing Reveals Many Cyclopeptides in the Human Gut and Other Environments (2020-01-22, Cell Systems)

Abstract

Cyclic and branch cyclic peptides (cyclopeptides) represent an important class of bioactive natural products that include many antibiotics and anti-tumor compounds. However, little is known about cyclopeptides in the human gut, despite the fact that humans are constantly exposed to them. To address this bottleneck, we developed the CycloNovo algorithm for de novo cyclopeptide sequencing that employs de Bruijn graphs, the workhorse of DNA sequencing algorithms. CycloNovo reconstructed many new cyclopeptides that we validated with transcriptome, metagenome, and genome mining analyses. Our benchmarking revealed a vast hidden cyclopeptidome in the human gut and other environments and suggested that CycloNovo offers a much-needed step-change for cyclopeptide discovery. Furthermore, CycloNovo revealed a wealth of anti-microbial cyclopeptides from food that survive the complete human gastrointestinal tract, raising the question of how these cyclopeptides might affect the human microbiome.\n\nSIGNIFICANCEThe golden age of antibiotics was followed by a decline in the pace of antibiotics discovery in the 1990s. The key prerequisite for the resurgence of antibiotics research is the development of a computational discovery pipeline for antibiotics sequencing. We describe such pipeline for cyclic and branch cyclic peptides (cyclopeptides) that represent an important class of bioactive natural products such as antibiotics and anti-tumor compounds. Our CycloNovo algorithm for cyclopeptide sequencing reconstructed many new cyclopeptides that we validated with transcriptome, metagenome, and genome mining analyses. CycloNovo revealed a wealth of anti-microbial cyclopeptides from food that survive the complete human gastrointestinal tract, raising the question of how these cyclopeptides might affect the human microbiome.

Authors

  1. Bahar Behsaz · University of California San Diego
  2. Hosein Mohimani · Carnegie Mellon University, University of California San Diego
  3. Alexey Gurevich · St Petersburg University, St. Petersburg State University
  4. Andrey Prjibelski · St Petersburg University, St. Petersburg State University
  5. Mark Fisher · ARC Centre of Excellence in Plant Energy Biology, University of Western Australia
  6. Larry Smarr · University of California San Diego
  7. Pieter C. Dorrestein · Scripps Institution of Oceanography, University of California San Diego, University of California System
  8. Joshua S. Mylne · ARC Centre of Excellence in Plant Energy Biology, University of Western Australia
  9. Pavel A. Pevzner · Max Planck Institute of Molecular Cell Biology and Genetics, Saint Petersburg Academic University, St Petersburg University, St. Petersburg State University, University of California San Diego, University of Southern California

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