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.


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).

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*


  • Peptides, Cyclic