Evidence map›Paper›PMID 35941113›Full record

ArticleNature communications2022

Native metabolomics identifies the rivulariapeptolide family of protease inhibitors.

Raphael Reher, Allegra T Aron, Pavla Fajtová, Paolo Stincone, Berenike Wagner, Alicia I Pérez-Lorente, Chenxi Liu, Ido Y Ben Shalom, Wout Bittremieux, Mingxun Wang and 18 more

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Article
  2. A Functional Metabolomics Framework to Track Microbiome Drug Metabolism.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
  5. Deciphering guanidine assimilation and riboswitch-based gene regulation in cyanobacteria for synthetic biology applications.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Native metabolomics identifies pteridines as CutA ligands and modulators of copper binding.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Dissecting the structural heterogeneity of proteins by native mass spectrometry.Protein science : a publication of the Protein Society · 2023
    Review
  19. Peptidomics.Nature reviews. Methods primers · 2023
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Raphael ReherScripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA.
Allegra T AronSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.
Pavla FajtováSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.
Paolo StinconeCluster of Excellence "Controlling Microbes to Fight Infections" (CMFI), University of Tuebingen, Tuebingen, Germany.
Berenike WagnerCluster of Excellence "Controlling Microbes to Fight Infections" (CMFI), University of Tuebingen, Tuebingen, Germany.
Alicia I Pérez-LorenteInstituto de Hortofruticultura Subtropical y Mediterránea "La Mayora," Consejo Superior de Investigaciones Científicas, Departamento de Microbiología, Universidad de Málaga, Málaga, Spain.
Chenxi LiuSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.
Ido Y Ben ShalomSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-7237-1690
Wout BittremieuxSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-3105-1359
Mingxun WangSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.
Kyowon JeongApplied Bioinformatics, Computer Science Department, University of Tuebingen, Tuebingen, Germany.ORCID 0000-0003-3776-3098
Marie L Matos-HernandezDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico.ORCID 0000-0003-0332-0942
Kelsey L AlexanderScripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA.
Eduardo J Caro-DiazDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico.ORCID 0000-0002-2049-6248
C Benjamin NamanLi Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, China.ORCID 0000-0002-4361-506X
J H William ScanlanDepartment of Pharmaceutical Chemistry and Center for Tumor Biology and Immunology (ZTI), University of Marburg, Marburg, Germany.
Phil M M HochbanDepartment of Pharmaceutical Chemistry and Center for Tumor Biology and Immunology (ZTI), University of Marburg, Marburg, Germany.
Wibke E DiederichDepartment of Pharmaceutical Chemistry and Center for Tumor Biology and Immunology (ZTI), University of Marburg, Marburg, Germany.
Carlos Molina-SantiagoInstituto de Hortofruticultura Subtropical y Mediterránea "La Mayora," Consejo Superior de Investigaciones Científicas, Departamento de Microbiología, Universidad de Málaga, Málaga, Spain.ORCID 0000-0002-1131-8917
Diego RomeroInstituto de Hortofruticultura Subtropical y Mediterránea "La Mayora," Consejo Superior de Investigaciones Científicas, Departamento de Microbiología, Universidad de Málaga, Málaga, Spain.ORCID 0000-0002-2052-6515
Khaled A SelimCluster of Excellence "Controlling Microbes to Fight Infections" (CMFI), University of Tuebingen, Tuebingen, Germany.ORCID 0000-0002-2974-9483
Peter SassCluster of Excellence "Controlling Microbes to Fight Infections" (CMFI), University of Tuebingen, Tuebingen, Germany.ORCID 0000-0002-4477-2382
Heike Brötz-OesterheltCluster of Excellence "Controlling Microbes to Fight Infections" (CMFI), University of Tuebingen, Tuebingen, Germany.ORCID 0000-0001-9364-1832
Chambers C HughesCluster of Excellence "Controlling Microbes to Fight Infections" (CMFI), University of Tuebingen, Tuebingen, Germany.ORCID 0000-0002-7000-6438
Pieter C DorresteinSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-3003-1030
Anthony J O'DonoghueSkaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA, USA.
William H GerwickScripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA. wgerwick@health.ucsd.edu.ORCID 0000-0003-1403-4458
Daniel PetrasScripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA. daniel.petras@uni-tuebingen.de.ORCID 0000-0002-6561-3022

Funding

TrainingP41GM103484 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BANDEIRA, NUNO · 2012 to 2018
$8.7M
Unified Computation Tools for Natural Products ResearchR01GM107550 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COTTRELL, GARRISON W, GERWICK, WILLIAM HENRY · 2013 to 2025
$8.2M
Reuse of Public Metabolomics DataR03CA211211 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DORRESTEIN, PIETER C · 2016 to 2016
$155k
NCI NIH HHS R03 CA211211NIGMS NIH HHS P41 GM103484NIGMS NIH HHS R01 GM107550
6 · The paper itself

Abstract

The identity and biological activity of most metabolites still remain unknown. A bottleneck in the exploration of metabolite structures and pharmaceutical activities is the compound purification needed for bioactivity assignments and downstream structure elucidation. To enable bioactivity-focused compound identification from complex mixtures, we develop a scalable native metabolomics approach that integrates non-targeted liquid chromatography tandem mass spectrometry and detection of protein binding via native mass spectrometry. A native metabolomics screen for protease inhibitors from an environmental cyanobacteria community reveals 30 chymotrypsin-binding cyclodepsipeptides. Guided by the native metabolomics results, we select and purify five of these compounds for full structure elucidation via tandem mass spectrometry, chemical derivatization, and nuclear magnetic resonance spectroscopy as well as evaluation of their biological activities. These results identify rivulariapeptolides as a family of serine protease inhibitors with nanomolar potency, highlighting native metabolomics as a promising approach for drug discovery, chemical ecology, and chemical biology studies.

Indexed as

MetabolomicsProtease InhibitorsChromatography, LiquidMagnetic Resonance SpectroscopyTandem Mass SpectrometryProtease Inhibitors

Identifiers

PMID35941113
PMCPMC9358669

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.