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Serine catabolism produces ROS, sensitizes cells to actin dysfunction, and suppresses cell growth in fission yeast

The Journal of Antibiotics volume 73, pages 574–580 (2020)Cite this article

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Abstract

Serine is an essential component in organisms as a building block of biomolecules, a precursor of metabolites, an allosteric regulator of an enzyme, etc. This amino acid is thought to be a key metabolite in human diseases including cancers and infectious diseases. To understand the consequence of serine catabolism, we screened natural products to identify a fungal metabolite chaetoglobosin D (ChD) as a specific inhibitor of fission yeast cell growth when cultivated with serine as a sole nitrogen source. ChD targets actin, and actin mutant cells showed severe growth defect on serine medium. ROS accumulated in cells when cultivated in serine medium, while actin mutant cells showed increased sensitivity to oxidative stress. ROS production is a new aspect of serine metabolism, which might be involved in disease progression, and actin could be the drug target for curing serine-dependent symptoms.

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Acknowledgements

We thank J. Ishiguro (Konan University), M. Balasubramanian (University of Warwick) and National Bio-Resource Project of the MEXT, Japan for yeast strains, and M. Sasaki (The University of Tokyo) for reading the paper. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (26102726 (SN), 17H06401 (HK and SN), 19H02840 (HK)) and Japan Society for the Promotion of Science (19H05640 (SN and MY)).

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Authors and Affiliations

  1. Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan

    Akihiko Kanou, Shinichi Nishimura & Hideaki Kakeya

  2. Department of Biotechnology, The University of Tokyo, Tokyo, 113-8657, Japan

    Shinichi Nishimura, Toshitsugu Tabuchi, Akihisa Matsuyama & Minoru Yoshida

  3. Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, 113-8657, Japan

    Shinichi Nishimura & Minoru Yoshida

  4. Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Saitama, 351-0198, Japan

    Shinichi Nishimura, Akihisa Matsuyama & Minoru Yoshida

  5. Research & Development Division, MicroBiopharm Japan Co., Ltd., 156 Nakagawara, Kiyosu-shi, Aichi, 452-0915, Japan

    Taira Kato

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  1. Akihiko Kanou
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  2. Shinichi Nishimura
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Correspondence to Shinichi Nishimura or Hideaki Kakeya.

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This work is dedicated to Professor William Fenical for his great contribution to marine natural products chemistry.

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Kanou, A., Nishimura, S., Tabuchi, T. et al. Serine catabolism produces ROS, sensitizes cells to actin dysfunction, and suppresses cell growth in fission yeast. J Antibiot 73, 574–580 (2020). https://doi.org/10.1038/s41429-020-0305-6

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  • DOI: https://doi.org/10.1038/s41429-020-0305-6

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