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The methylerythritol phosphate pathway as an oxidative stress sense and response system

Author

Listed:
  • Jordi Perez-Gil

    (Queensland University of Technology
    Queensland University of Technology
    Queensland University of Technology)

  • James Behrendorff

    (Queensland University of Technology
    Queensland University of Technology
    Queensland University of Technology)

  • Andrew Douw

    (Queensland University of Technology
    The University of Queensland)

  • Claudia E. Vickers

    (Queensland University of Technology
    Queensland University of Technology
    Queensland University of Technology
    BioBuilt Solutions)

Abstract

The methylerythritol phosphate (MEP) pathway is responsible for biosynthesis of the precursors of isoprenoid compounds in eubacteria and plastids. It is a metabolic alternative to the well-known mevalonate pathway for isoprenoid production found in archaea and eukaryotes. Recently, a role for the MEP pathway in oxidative stress detection, signalling, and response has been identified. This role is executed in part through the unusual cyclic intermediate, methylerythritol cyclodiphosphate (MEcDP). We postulate that this response is triggered through the oxygen sensitivity of the MEP pathway’s terminal iron-sulfur (Fe-S) cluster enzymes. MEcDP is the substrate of IspG, the first Fe-S cluster enzyme in the pathway; it accumulates under oxidative stress conditions and acts as a signalling molecule. It may also act as an antioxidant. Furthermore, evidence is emerging for a broader and highly nuanced role of the MEP pathway in oxidative stress responses, implemented through a complex system of differential regulation and sensitivity at numerous nodes in the pathway. Here, we explore the evidence for such a role (including the contribution of the Fe-S cluster enzymes and different pathway metabolites, especially MEcDP), the evolutionary implications, and the many questions remaining about the behaviour of the MEP pathway in the presence of oxidative stress.

Suggested Citation

  • Jordi Perez-Gil & James Behrendorff & Andrew Douw & Claudia E. Vickers, 2024. "The methylerythritol phosphate pathway as an oxidative stress sense and response system," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49483-8
    DOI: 10.1038/s41467-024-49483-8
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    References listed on IDEAS

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    1. Igor W. Bogorad & Tzu-Shyang Lin & James C. Liao, 2013. "Synthetic non-oxidative glycolysis enables complete carbon conservation," Nature, Nature, vol. 502(7473), pages 693-697, October.
    2. Jishan Jiang & Cecilia Rodriguez-Furlan & Jin-Zheng Wang & Amancio de Souza & Haiyan Ke & Taras Pasternak & Hanna Lasok & Franck A. Ditengou & Klaus Palme & Katayoon Dehesh, 2018. "Interplay of the two ancient metabolites auxin and MEcPP regulates adaptive growth," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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