The undiscovered natural product potential of Actinomycetes
Actinomycetes have been a cornerstone species for the discovery of bioactive natural products with applications in pharmacotherapy and biotechnology. To expand the experimental evidence of their biosynthetic potential, we collected liquid-chromatography mass spectrometry untargeted metabolomics data on 948 microbial strains, mostly from Actinomycetes. This resulted in nearly two million MS/MS spectra, with an annotation rate of 13.3% corresponding to 2352 annotated molecules. Despite the efforts to link biosynthetic gene clusters to known molecules, most remain uncharacterized. This highlights the need for metabolomic data to bridge the gap between genomic potential and metabolite production. Although many unannotated spectra might correspond to different ion forms of the same molecule, the large amount of unknown molecules present in these datasets indicates that a significant number of natural products remain to be discovered, even within one of the most thoroughly studied sets of organisms. We provide a large metabolomics dataset as a public resource for data mining of microbial molecules and highlight its value by demonstrating the detection of edapochelins, recently discovered non-ribosomal peptides.
Authors
- Tiago Leão (ORCID: https://orcid.org/0000-0003-1034-9153)
- Yasin El Abiead (ORCID: https://orcid.org/0000-0003-4392-7706)
- Andrés Mauricio Caraballo‐Rodríguez
- Andrés Cumsille (ORCID: https://orcid.org/0000-0003-2087-7435)
- María Taboada-Alquerque (ORCID: https://orcid.org/0000-0003-0551-947X)
- Sarvar A. Kakhkhorov (ORCID: https://orcid.org/0000-0002-4698-8793)
- Hosein Mohimani (ORCID: https://orcid.org/0000-0003-3980-2505)
- Bahar Behsaz
- Sarolt Magyari
- Kirk Broders (ORCID: https://orcid.org/0000-0002-8569-6005)
- Beatriz Cámara (ORCID: https://orcid.org/0000-0001-5227-7499)
- Mengzhou Hu (ORCID: https://orcid.org/0000-0002-1571-8029)
- Louis‐Félix Nothias (ORCID: https://orcid.org/0000-0001-6711-6719)
- Pieter C. Dorrestein (ORCID: https://orcid.org/0000-0002-3003-1030)
- Vincent Charron‐Lamoureux (ORCID: https://orcid.org/0000-0001-9440-7036)
- Simone Zuffa (ORCID: https://orcid.org/0000-0001-7237-3402)
- Jason A. Clement (ORCID: https://orcid.org/0009-0009-4762-1983)
- Christopher Leone
Institutions
- Centre National de la Recherche Scientifique (FR)
- Agricultural Research Service (US)
- University of Cartagena (CO)
- University of California, Los Angeles (US)
- National Center for Agricultural Utilization Research (US)
- Tashkent University of Information Technology (UZ)
- Board of the Swiss Federal Institutes of Technology (CH)
- Wisconsin Institutes for Discovery (US)
- ETH Zurich (CH)
- University of California San Diego (US)
- Institut de Chimie de Nice (FR)
- Fondation Sophia Antipolis (FR)
- Baruch S. Blumberg Institute (US)
- University of Montana (US)
- Carnegie Mellon University (US)
- Federico Santa María Technical University (CL)
- Universidade Estadual Paulista (Unesp) (BR)
Publication Details
- Journal
- The Journal of Antibiotics
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1038/s41429-025-00876-x
- Citations
- 1
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.39
Funders
- U.S. Department of Agriculture
- Gordon and Betty Moore Foundation
- Universidad Técnica Federico Santa María
- Eidgenössische Technische Hochschule Zürich
- Agencia Nacional de Investigación y Desarrollo
- National Institutes of Health
- Agricultural Research Service
- National Cancer Institute
- Oak Ridge National Laboratory