2026-03-24 カリフォルニア大学リバーサイド校（UCR）
＜関連情報＞
- https://news.ucr.edu/articles/2026/03/24/how-plants-stop-growing-survive-stress
- https://www.pnas.org/doi/10.1073/pnas.2529243123
代謝産物による酵素活性の制御は、ストレスと生合成調節を結びつける Metabolite control of enzyme activity links stress to biosynthetic regulation
Wilhelmina van de Ven, Manhoi Hur, María Fernanda Gómez-Méndez, +5 , and Katayoon Dehesh
Proceedings of the National Academy of Sciences Published:February 4, 2026
DOI:https://doi.org/10.1073/pnas.2529243123
Significance
Metabolite-mediated feedback represents a rather unexplored mode of metabolic regulation in plants and other organisms. This study identifies methylerythritol cyclodiphosphate (MEcPP), an intermediate of the methylerythritol phosphate (MEP) pathway, as a dual-function metabolite that not only participates in isoprenoid biosynthesis and retrograde signaling but also directly modulates enzyme stability and activity. By destabilizing and inhibiting methylerythritol cytidylyltransferase (MCT), MEcPP enables rapid, transcription-independent control of pathway output in response to stress. These findings reveal a fundamental mechanism by which cells couple environmental adaptation with metabolic homeostasis. By uncovering how an internal metabolite governs plastidial enzyme activity, this work establishes a conceptual and mechanistic framework for engineering metabolic resilience and optimizing isoprenoid production.
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.
