Glutathione acts as an exometabolite that promotes growth recovery in fission yeast with defects in amino acid metabolism and cell polarity
8 affiliations
- 1Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
- 2Center for Sustainable Resource Science, RIKEN, Wako, Japan
- 3Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
- 4Engineering Biology Research Center, Kobe University, Kobe, Japan
- 5Faculty of science, Gakushuin University, Toshima-ku, Tokyo, Japan
- 6Office of University Professors, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
- 7Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
- 8Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan
Abstract
Microorganisms in nature form communities through diverse interactions, such as mutualism and competition, to adapt to their ecological environments. These interactions seem to be mediated by extracellular metabolites (exometabolites), yet the chemical and biological diversity underlying these processes remains largely unexplored. In this study, we examined the chemical basis of exometabolite-mediated interactions in the fission yeast Schizosaccharomyces pombe by a genome-wide screen employing 3,420 viable gene deletion mutants. We identified 37 strains that exhibited growth defects in monoculture on a minimal medium but exhibited growth recovery in the vicinity of wild-type colonies (co-culture), suggesting that exometabolites derived from wild-type cells compensated for the gene deletion. Both lipophilic and water-soluble fractions obtained by solvent partitioning of the wild-type culture supernatant promoted growth recovery. Among the 11 mutants rescued by the water-soluble fraction, 6 were cysteine auxotrophs, prompting analyses of thiol-containing metabolites by liquid chromatography-mass spectrometry (LC-MS), revealing the presence of glutathione (GSH) in the culture supernatant. GSH restored growth in most strains as a nutrient source. In contrast, GSH rescued cell morphology defects in the hob3∆ mutant, lacking the Bin/amphiphysin/Rvs (BAR) adaptor protein Hob3, through a mechanism independent of nutrition. This research advances understanding of exometabolite-mediated interactions in S. pombe by identifying GSH as an exometabolite that influences cellular processes and potentially shapes microbial communities.
IMPORTANCE: Microorganisms secrete a wide range of metabolites that control microbial community behavior. These extracellular metabolites (exometabolites) include not only well-studied signaling molecules but also diverse primary and secondary metabolites, suggesting complex interactions among microbes. However, the molecular basis of these interactions remains poorly understood, partly due to challenges in detecting them experimentally. In this study, we surveyed exometabolites involved in cell–cell interactions in the model eukaryotic microorganism Schizosaccharomyces pombe. S. pombe releases a wide variety of metabolites outside the cells, including previously reported nitrogen signaling factors (NSFs) and glutathione (GSH) identified in this work. By analyzing gene deletion mutants whose growth is supported by extracellular GSH, we provide new insights into how secreted primary exometabolites compensate for specific genetic defects and influence cell physiology in microbial populations.
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BibTeX
@article{yoshizumi2026glutathione,
title = {{Glutathione acts as an exometabolite that promotes growth recovery in fission yeast with defects in amino acid metabolism and cell polarity}},
author = {Ryotaro Yoshizumi and Shunichi Miura and Hiroaki Matoba and Go Hirai and Shumpei Asamizu and Hiroyasu Onaka and Yoko Yashiroda and Akihisa Matsuyama and Minoru Yoshida and Shinichi Nishimura},
journal = {mSystems},
year = {2026},
month = sep,
doi = {10.1128/msystems.00123-26},
url = {https://doi.org/10.1128/msystems.00123-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Glutathione acts as an exometabolite that promotes growth recovery in fission yeast with defects in amino acid metabolism and cell polarity
AU - Ryotaro Yoshizumi
AU - Shunichi Miura
AU - Hiroaki Matoba
AU - Go Hirai
AU - Shumpei Asamizu
AU - Hiroyasu Onaka
AU - Yoko Yashiroda
AU - Akihisa Matsuyama
AU - Minoru Yoshida
AU - Shinichi Nishimura
PY - 2026
DA - 2026/09/14
JO - mSystems
DO - 10.1128/msystems.00123-26
UR - https://doi.org/10.1128/msystems.00123-26
AB - Microorganisms in nature form communities through diverse interactions, such as mutualism and competition, to adapt to their ecological environments. These interactions seem to be mediated by extracellular metabolites (exometabolites), yet the chemical and biological diversity underlying these processes remains largely unexplored. In this study, we examined the chemical basis of exometabolite-mediated interactions in the fission yeast Schizosaccharomyces pombe by a genome-wide screen employing 3,420 viable gene deletion mutants. We identified 37 strains that exhibited growth defects in monoculture on a minimal medium but exhibited growth recovery in the vicinity of wild-type colonies (co-culture), suggesting that exometabolites derived from wild-type cells compensated for the gene deletion. Both lipophilic and water-soluble fractions obtained by solvent partitioning of the wild-type culture supernatant promoted growth recovery. Among the 11 mutants rescued by the water-soluble fraction, 6 were cysteine auxotrophs, prompting analyses of thiol-containing metabolites by liquid chromatography-mass spectrometry (LC-MS), revealing the presence of glutathione (GSH) in the culture supernatant. GSH restored growth in most strains as a nutrient source. In contrast, GSH rescued cell morphology defects in the hob3∆ mutant, lacking the Bin/amphiphysin/Rvs (BAR) adaptor protein Hob3, through a mechanism independent of nutrition. This research advances understanding of exometabolite-mediated interactions in S. pombe by identifying GSH as an exometabolite that influences cellular processes and potentially shapes microbial communities. IMPORTANCE: Microorganisms secrete a wide range of metabolites that control microbial community behavior. These extracellular metabolites (exometabolites) include not only well-studied signaling molecules but also diverse primary and secondary metabolites, suggesting complex interactions among microbes. However, the molecular basis of these interactions remains poorly understood, partly due to challenges in detecting them experimentally. In this study, we surveyed exometabolites involved in cell–cell interactions in the model eukaryotic microorganism Schizosaccharomyces pombe. S. pombe releases a wide variety of metabolites outside the cells, including previously reported nitrogen signaling factors (NSFs) and glutathione (GSH) identified in this work. By analyzing gene deletion mutants whose growth is supported by extracellular GSH, we provide new insights into how secreted primary exometabolites compensate for specific genetic defects and influence cell physiology in microbial populations.
SN - 2379-5077
ER -