ArticleProceedings of the National Academy of Sciences of the United States of America2026
Metabolite control of enzyme activity links stress to biosynthetic regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Phytol in Skin Care: From Multidimensional Pharmacological Mechanisms to Nanocarrier-Based Cosmetic Applications.International journal of molecular sciences · 2026Review
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Authors and funding
9 authors.
Funding
Abstract
Cells must continuously adjust metabolic output to maintain homeostasis under changing environmental conditions, yet the mechanisms that enable rapid and reversible control of pathway activity remain largely unknown. The methylerythritol phosphate (MEP) pathway, of bacterial origin and conserved in plastid-bearing eukaryotes, including plants and apicomplexan parasites, produces isoprenoid precursors essential for growth and stress adaptation. Here, we identify methylerythritol cyclodiphosphate (MEcPP) as a dual-function metabolite that serves both as a biosynthetic intermediate and a direct modulator of enzyme activity. Genetic perturbations and high light stress revealed step-specific MEcPP accumulation independent of transcriptional regulation. Biochemical and protease-protection assays showed that MEcPP destabilizes and inhibits methylerythritol cytidylyltransferase (MCT) while modestly stabilizing hydroxymethylbutenyl diphosphate synthase (HDS). Molecular docking analyses indicate that MEcPP interacts directly with the MCT catalytic site, displacing the natural substrate and thereby attenuating enzyme activity, suggesting a competitive, feedback-like mechanism of metabolic control. These results define MEcPP as a metabolic feedback signal that translates stress-induced changes into targeted enzymatic control. This mechanism illustrates how pathway intermediates dynamically coordinate biosynthetic activity with environmental cues, representing a broadly conserved strategy for metabolite-driven control of cellular metabolism.
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