Chemical richness and diversity of uncultivated ‘Entotheonella’ symbionts in marine sponges
Marine sponges are the source of numerous bioactive natural products that serve as chemical defenses and provide pharmaceutical leads for drug development. For some of the compounds, symbiotic bacteria have been established as the actual producers. Among the known sponge symbionts, 'Candidatus Entotheonella' members stand out because of their abundant and variable biosynthetic gene clusters (BGCs). Here, to obtain broader insights into this producer taxon, we conduct a comparative analysis on eight sponges through metagenomic and single-bacterial sequencing and biochemical studies. The data suggest sets of biosynthetic genes that are largely unique in 14 'Entotheonella' candidate species and a member of a sister lineage named 'Candidatus Proxinella'. Four biosynthetic loci were linked in silico or experimentally to cytotoxins, antibiotics and the terpene cembrene A from corals. The results support widespread and diverse bacterial roles in the chemistry of sponges and aid the development of sustainable production methods for sponge-derived therapeutics.
Authors
- Shirley A. Pomponi (ORCID: https://orcid.org/0000-0003-4982-1515)
- Amy E. Wright (ORCID: https://orcid.org/0000-0003-4872-9776)
- Alena B. Streiff (ORCID: https://orcid.org/0000-0003-3635-5113)
- Detmer Sipkema (ORCID: https://orcid.org/0000-0003-3836-219X)
- Karen Co Tan (ORCID: https://orcid.org/0000-0002-6740-9412)
- Jörn Piel (ORCID: https://orcid.org/0000-0002-2282-8154)
- Jörn Kalinowski (ORCID: https://orcid.org/0000-0002-9052-1998)
- Kentaro Takada (ORCID: https://orcid.org/0000-0003-3835-1482)
- Mohammad Alanjary (ORCID: https://orcid.org/0000-0001-8420-1325)
- Haruko Takeyama (ORCID: https://orcid.org/0000-0002-2058-8185)
- Tomohisa Kuzuyama (ORCID: https://orcid.org/0000-0002-7221-5858)
- Masato Kogawa
- Christoph Meier (ORCID: https://orcid.org/0000-0002-4212-3493)
- Ikuro Abe (ORCID: https://orcid.org/0000-0002-3640-888X)
- Michelle Schorn (ORCID: https://orcid.org/0000-0001-8144-6052)
- Jackson K. B. Cahn (ORCID: https://orcid.org/0000-0001-8849-4516)
- Christian Rückert (ORCID: https://orcid.org/0000-0002-9722-4435)
- Yuito Yamada
- Yoko Egami
- Eike E. Peters (ORCID: https://orcid.org/0000-0003-2948-2915)
- Toshiyuki Wakimoto (ORCID: https://orcid.org/0000-0003-2917-1797)
- Hiromi Yokoyama (ORCID: https://orcid.org/0009-0008-4991-896X)
- Christopher R. Field (ORCID: https://orcid.org/0000-0002-8305-7728)
- Paco Cárdenas (ORCID: https://orcid.org/0000-0003-4045-6718)
- Alessandro Lotti
- Yu Nakashima (ORCID: https://orcid.org/0000-0001-7788-8333)
- Maria Dell (ORCID: https://orcid.org/0000-0003-2718-2409)
- Taro Shiraishi (ORCID: https://orcid.org/0000-0002-6540-8029)
Institutions
- Uppsala University (SE)
- Waseda University (JP)
- Bielefeld University (DE)
- The Open University of Japan (JP)
- Hokkaido University (JP)
- Hokkaido Pharmaceutical University (JP)
- Board of the Swiss Federal Institutes of Technology (CH)
- Florida Atlantic University (US)
- Kitasato University (JP)
- Harbor Branch Oceanographic Institute (US)
- The University of Tokyo (JP)
- Wageningen University & Research (NL)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2025-11-13
- DOI
- https://doi.org/10.1038/s41589-025-02066-0
- Citations
- 2
- Primary Topic
- Marine Sponges and Natural Products
- Type
- article
- Field-Weighted Citation Impact
- 2.47
Funders
- National Science Foundation
- Gordon and Betty Moore Foundation
- Institut Français de Recherche pour l'Exploitation de la Mer
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eidgenössische Technische Hochschule Zürich
- Muséum National d'Histoire Naturelle
- Japan Society for the Promotion of Science
- Functional Genomics Center Zurich