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The coculture of Fomitopsis betulina with Escherichia coli induces a nutritional stress and triggers secondary metabolism pathways.

  1. 1Institut National de Recherche pour l'Agriculture l'Alimentation et l'Environnement Departement MICA

Abstract

Basidiomycete fungi are an underexplored source of specialized metabolites with significant biotechnological potential. However, the environmental cues that activate their biosynthetic pathways remain poorly understood. Here, we investigated the response of the wood-decaying fungus Fomitopsis betulina, to nutritional competition using co-cultures with Escherichia coli. On solid medium, F. betulina inhibited the bacterial growth. Using a mass spectrometry-based metabolomics approach, we identified a Sumikis acid derivative, calcium diformate, and sulfuric acid among the compounds enriched within the inhibition zone and hypothesized that these compounds were associated with the acidification of the medium. Although F. betulina has previously been reported to produce the antibacterial compound piptamine, neither piptamine nor related derivatives were detected under our experimental conditions. In liquid medium, the co-culture with E. coli caused the rapid depletion of the available glucose, resulting in the establishment of carbon-starvation conditions and a 44% reduction in fungal biomass. Transcriptomic analyses revealed extensive metabolic reprogramming in response to bacterial competition, including the induction of genes involved in carbon acquisition, nutrient transport, redox homeostasis, and stress adaptation. Notably, a homolog of the Velvet regulatory complex, a central regulator of fungal development and specialized metabolism, was upregulated. The co-culture induced the expression of genes associated with multiple biosynthetic gene clusters, including terpene, polyketide, and fungal RiPP. Taken together, our results demonstrate that bacterial competition acts as a potent trigger of nutritional stress and secondary metabolism in F. betulina. More broadly, fungal-bacterial co-culture represents a promising alternative to extractions to identify high-value added metabolites pathways from basidiomycetes.

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BibTeX
@misc{albert2026coculture,
  title = {{The coculture of Fomitopsis betulina with Escherichia coli induces a nutritional stress and triggers secondary metabolism pathways.}},
  author = {Q. ALBERT and E. Drula and J. LAMBERT and I. Herpoël-Gimbert and D. Navarro and P. VILELLA and M. MARESCA and A. D. MAIO and M. ROBIN and M. Lafond and S. GREFF and M.-N. Rosso},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.14.751415},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751415v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - The coculture of Fomitopsis betulina with Escherichia coli induces a nutritional stress and triggers secondary metabolism pathways.
AU  - Q. ALBERT
AU  - E. Drula
AU  - J. LAMBERT
AU  - I. Herpoël-Gimbert
AU  - D. Navarro
AU  - P. VILELLA
AU  - M. MARESCA
AU  - A. D. MAIO
AU  - M. ROBIN
AU  - M. Lafond
AU  - S. GREFF
AU  - M.-N. Rosso
PY  - 2026
DA  - 2026/09/14
PB  - bioRxiv
DO  - 10.64898/2026.09.14.751415
UR  - https://www.biorxiv.org/content/10.64898/2026.09.14.751415v1
AB  - Basidiomycete fungi are an underexplored source of specialized metabolites with significant biotechnological potential. However, the environmental cues that activate their biosynthetic pathways remain poorly understood. Here, we investigated the response of the wood-decaying fungus Fomitopsis betulina, to nutritional competition using co-cultures with Escherichia coli. On solid medium, F. betulina inhibited the bacterial growth. Using a mass spectrometry-based metabolomics approach, we identified a Sumikis acid derivative, calcium diformate, and sulfuric acid among the compounds enriched within the inhibition zone and hypothesized that these compounds were associated with the acidification of the medium. Although F. betulina has previously been reported to produce the antibacterial compound piptamine, neither piptamine nor related derivatives were detected under our experimental conditions. In liquid medium, the co-culture with E. coli caused the rapid depletion of the available glucose, resulting in the establishment of carbon-starvation conditions and a 44% reduction in fungal biomass. Transcriptomic analyses revealed extensive metabolic reprogramming in response to bacterial competition, including the induction of genes involved in carbon acquisition, nutrient transport, redox homeostasis, and stress adaptation. Notably, a homolog of the Velvet regulatory complex, a central regulator of fungal development and specialized metabolism, was upregulated. The co-culture induced the expression of genes associated with multiple biosynthetic gene clusters, including terpene, polyketide, and fungal RiPP. Taken together, our results demonstrate that bacterial competition acts as a potent trigger of nutritional stress and secondary metabolism in F. betulina. More broadly, fungal-bacterial co-culture represents a promising alternative to extractions to identify high-value added metabolites pathways from basidiomycetes.
ER  -