A yeast mating platform for multiplex screening of fungal GPCR–ligand interactions

G Giovanni Schiesaro (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) M Melani Mariscal (Departamento de Genética, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba) M Mathias Jönsson (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) R Ricardo Tenente (Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen) M Mathies Brinks Sørensen (Department of Applied Mathematics and Computer Science, Technical University of Denmark) M Marcus Wäneskog (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) M María Victoria Aguilar-Pontes (Departamento de Genética, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba) A Agustina Undabarrena (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) M Marcus Deichmann (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) E Emma E. Hoch-Schneider (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) V Viji Kandasamy (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) T Thomas M. Frimurer A Antonio Di Pietro (Departamento de Genética, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba) L Line Katrine Harder Clemmensen (Department of Applied Mathematics and Computer Science, Technical University of Denmark) M Michael Krogh Jensen (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark) E Emil Damgaard Jensen (Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark)

Abstract

Fungi are essential members across ecosystems, yet phytopathogenic fungi pose an increasing risk to crop yields. Despite their ecologic importance, cell–cell communication in fungi is underexplored, partly due to the lack of high-throughput techniques. Here, we developed a Yeast Mating Platform (YeMaP) to investigate the interaction between fungal G protein–coupled receptors (GPCRs) and pheromone peptides. We used YeMaP for high-throughput screening of 8,000 pheromone sequences and identified peptides with improved agonism or antagonism action. We found that these peptides can be applied in a native fungal system such as the plant pathogen Fusarium oxysporum , to control hyphal chemotropism and reduce plant root penetration. Additionally, we utilized YeMaP in a one-pot assay to investigate how abiotic factors influence the communication of multiple pheromone–GPCR combinations and found that the cell–cell communication mediated by the GPCR Ste2 from F. oxysporum signaled robustly across different abiotic factors, while other fungal GPCR–pheromone interactions were more sensitive to changes. Taken together, YeMaP accelerates the identification of fungal GPCR–peptide interactions by enabling one-pot assays, and serves as a model system for studying fungal cell–cell communication.

Article Details

Volume / Issue Vol. 122, Issue 43
Published October 28, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (16)

G

Giovanni Schiesaro

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

M

Melani Mariscal

Departamento de Genética, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba

M

Mathias Jönsson

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

R

Ricardo Tenente

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen

M

Mathies Brinks Sørensen

Department of Applied Mathematics and Computer Science, Technical University of Denmark

M

Marcus Wäneskog

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

M

María Victoria Aguilar-Pontes

Departamento de Genética, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba

A

Agustina Undabarrena

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

M

Marcus Deichmann

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

E

Emma E. Hoch-Schneider

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

V

Viji Kandasamy

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

T

Thomas M. Frimurer

A

Antonio Di Pietro

Departamento de Genética, Campus de Excelencia Internacional Agroalimentario, Universidad de Córdoba

L

Line Katrine Harder Clemmensen

Department of Applied Mathematics and Computer Science, Technical University of Denmark

M

Michael Krogh Jensen

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

E

Emil Damgaard Jensen

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark