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PreprintCited by 1Microbial Natural Products and BiosynthesisAntimicrobial Peptides and ActivitiesChemical Synthesis and Analysis

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Rules of Coexistence: RiPP Recognition Elements Evolved to Prevent Pathway Interference through Leader Peptide Discrimination

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Dubiley, Svetlana, Popov, Aleksandr, Bikmetov, Dmitriy, Grigoreva, Anastasia, Serebryakova, Marina, Severinov, Konstantin, Lippens, Guy, Wada, Akira, Tagami, Shunsuke·2025·Nature Communications
DOI 10.21203/rs.3.rs-7990798/v1PMC PMC13381572

Preprint — published as 10.1038/s41467-026-73250-6

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Abstract

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are natural products with diverse structures and functions. Here, we report the discovery of a new family of RiPPs, named linear polyphosphorylated peptides (LPPs). Their biosynthetic gene clusters are widespread in the Bacillota genomes and often co-localize with those of lasso peptides, a distinct class of RiPPs. Both LPP and lasso peptide biosyntheses rely on specific interactions between precursor peptides and small adapter protein domains known as RiPP recognition elements (RREs). Since LPP and lasso peptide precursors share a conserved RRE-binding motif, conflicts between the two biosynthetic pathways may emerge. Through biochemical and structural studies, we reveal how the two RiPP systems evolved to discriminate between their cognate precursors and leader peptidases, allowing them to coexist within a single host. Thus, our study provides new insights into the evolutionary diversification of RiPP families.

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Metadata

Authors
Dubiley, S., Popov, A., Bikmetov, D., Grigoreva, A., Serebryakova, M., Severinov, K., Lippens, G., Wada, A., & Tagami, S.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • RIKEN Center for Integrative Medical Sciences (JP)
  • Institute of Gene Biology, Russian Academy of Science
  • Lomonosov Moscow State University (RU)
  • Russian Academy of Sciences (RU)
Corresponding author
  • Dubiley, Svetlana
  • Tagami, Shunsuke
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-11-13
Volume
17
Issue
1
ISSN
2041-1723 (ISSN-L)
DOI
10.21203/rs.3.rs-7990798/v1
PMC
PMC13381572
OpenAlex
W7161770478
Cited by
1
References
1
Citations by year
2026: 1
FWCI
4.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Agence Nationale de la Recherche (France2030, ANR-25-CE44-1111, ANR-24-RRII-0003, ANR-11-INBS, ANR-11-INBS-0010)
  • Russian Science Foundation
  • Muséum National d'Histoire Naturelle (ANR-11-INBS-)
  • Institute Pasteur De Lille
  • Lomonosov Moscow State University
  • Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
  • University of Illinois at Urbana-Champaign
  • RIKEN
Topics
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Keywords
ribosomally synthesized and post-translationally modified peptides, lasso peptides, leader peptidase, biosynthetic gene clusters, Firmicutes, natural products
MeSH terms
Amino Acid Sequence, Multigene Family, Peptides, Protein Processing, Post-Translational, Ribosomes, Evolution, Molecular, Protein Sorting Signals

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