ArticleACS chemical biology2012
2C-Methyl-d-erythritol 4-phosphate enhances and sustains cyclodiphosphate synthase IspF activity.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Harnessing evolution: leveraging bacterial isoprenoid pathway diversity toward improved bioengineering strategies.Journal of bacteriology · 2026Review
- The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility inbioRxiv : the preprint server for biology · 2025Article
- The methylerythritol phosphate pathway as an oxidative stress sense and response system.Nature communications · 2024Review
- Biosynthesis Progress of High-Energy-Density Liquid Fuels Derived from Terpenes.Microorganisms · 2024Review
- HDR, the last enzyme in the MEP pathway, differently regulates isoprenoid biosynthesis in two woody plants.Plant physiology · 2023Article
- The Multifaceted MEP Pathway: Towards New Therapeutic Perspectives.Molecules (Basel, Switzerland) · 2023Review
- Alternative metabolic pathways and strategies to high-titre terpenoid production inNatural product reports · 2022Review
- Retracted: Exploring Drug Targets in Isoprenoid Biosynthetic Pathway forBiochemistry research international · 2022Article
- Structural and biophysical characterization of the Burkholderia pseudomallei IspF inhibitor L-tryptophan hydroxamate.Bioorganic & medicinal chemistry letters · 2021Article
- Positioning Bacillus subtilis as terpenoid cell factory.Journal of applied microbiology · 2021Review
- Diversifying Isoprenoid PlatformsFrontiers in microbiology · 2021Review
- Combinatorial Methylerythritol Phosphate Pathway Engineering and Process Optimization for Increased Menaquinone-7 Synthesis inJournal of microbiology and biotechnology · 2020Article
- Investigation of the methylerythritol 4-phosphate pathway for microbial terpenoid production through metabolic control analysis.Microbial cell factories · 2019Article
- Antibacterial activity of 2-amino-4-hydroxypyrimidine-5-carboxylates and binding to Burkholderia pseudomallei 2-C-methyl-d-erythritol-2,4-cyclodiphosphate synthase.Bioorganic & medicinal chemistry letters · 2019Article
- EngineeredFrontiers in microbiology · 2019Article
- The Methylerythritol Phosphate Pathway: Promising Drug Targets in the Fight against Tuberculosis.ACS infectious diseases · 2018Review
- Engineering metabolic pathways inSynthetic and systems biotechnology · 2018Article
- Hydroxybenzaldoximes Are D-GAP-Competitive Inhibitors of E. coli 1-Deoxy-D-Xylulose-5-Phosphate Synthase.Chembiochem : a European journal of chemical biology · 2015Article
- A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis.Antimicrobial agents and chemotherapy · 2015Article
- Isoprenoid metabolism in apicomplexan parasites.Current clinical microbiology reports · 2014Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
There is significant progress toward understanding catalysis throughout the essential MEP pathway to isoprenoids in human pathogens; however, little is known about pathway regulation. The present study begins by testing the hypothesis that isoprenoid biosynthesis is regulated via feedback inhibition of the fifth enzyme cyclodiphosphate synthase IspF by downstream isoprenoid diphosphates. Here, we demonstrate recombinant E. coli IspF is not inhibited by downstream metabolites isopentenyl diphosphate (IDP), dimethylallyl diphosphate (DMADP), geranyl diphosphate (GDP), and farnesyl diphosphate (FDP) under standard assay conditions. However, 2C-methyl-d-erythritol 4-phosphate (MEP), the product of reductoisomerase IspC and first committed MEP pathway intermediate, activates and sustains this enhanced IspF activity, and the IspF-MEP complex is inhibited by FDP. We further show that the methylerythritol scaffold itself, which is unique to this pathway, drives the activation and stabilization of active IspF. Our results suggest a novel feed-forward regulatory mechanism for 2C-methyl-d-erythritol 2,4-cyclodiphosphate (MEcDP) production and support an isoprenoid biosynthesis regulatory mechanism via feedback inhibition of the IspF-MEP complex by FDP. The results have important implications for development of inhibitors against the IspF-MEP complex, which may be the physiologically relevant form of the enzyme.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.