ArticleThe Journal of biological chemistry2013
Feedback inhibition of deoxy-D-xylulose-5-phosphate synthase regulates the methylerythritol 4-phosphate pathway.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 185 citations in OpenAlex.
- Chorismate and isochorismate turnover reveal hidden dynamics of aromatic metabolism in Arabidopsis leaves.The Plant cell · 2026Article
- Beyond Tanacetum cinerariifolium: Advances in Pyrethrins Biosynthesis and Prospects for Engineered Cell Factories.Molecular biotechnology · 2026Review
- CHASE-independent cytokinin perception triggers 3',5'-cAMP signaling inJournal of bacteriology · 2026Article
- Harnessing evolution: leveraging bacterial isoprenoid pathway diversity toward improved bioengineering strategies.Journal of bacteriology · 2026Review
- Engineering Cyanobacteria for High-Yield Photosynthetic Isoprene Production With Long-Term Phenotypic Stability.Plant biotechnology journal · 2026Article
- Strategic selection of microbial cell factories for sustainable and application-specific terpenoid production.Frontiers in bioengineering and biotechnology · 2026Review
- Leveraging a synthetic biology approach to enhance BCG-mediated expansion of Vγ9Vδ2 T cells.PloS one · 2026Article
- Multi-omics integration reveals tissue-specific biosynthesis of sesquiterpenoids in the medicinal plant Eupatorium lindleyanum.PloS one · 2026Article
- The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility inJournal of bacteriology · 2025Article
- The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility inbioRxiv : the preprint server for biology · 2025Article
- Rubisco supplies pyruvate for the 2-C-methyl-D-erythritol-4-phosphate pathway.Nature plants · 2024Article
- A picomolar inhibitor of theAntimicrobial agents and chemotherapy · 2024Article
- Deoxyxylulose 5-Phosphate Synthase Does Not Play a Major Role in Regulating the Methylerythritol 4-Phosphate Pathway in Poplar.International journal of molecular sciences · 2024Article
- Recent Advances in Chemistry and Antioxidant/Anticancer Biology of Monoterpene and Meroterpenoid Natural Product.Molecules (Basel, Switzerland) · 2024Review
- Cloning and Functional Characterization of 2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase (LiMCT) Gene in Oriental Lily (Lilium 'Sorbonne').Molecular biotechnology · 2024Article
- Hydroxymethylbutenyl diphosphate accumulation reveals MEP pathway regulation for high COProceedings of the National Academy of Sciences of the United States of America · 2023Article
- HDR, the last enzyme in the MEP pathway, differently regulates isoprenoid biosynthesis in two woody plants.Plant physiology · 2023Article
- MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply.Plant communications · 2023Article
- A systematic overexpression approach reveals native targets to increase squalene production inFrontiers in plant science · 2023Article
- Evolutionary flexibility and rigidity in the bacterial methylerythritol phosphate (MEP) pathway.Frontiers in microbiology · 2023Article
17 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway leads to the biosynthesis of isopentenyl diphosphate (IDP) and dimethylallyl diphosphate (DMADP), the precursors for isoprene and higher isoprenoids. Isoprene has significant effects on atmospheric chemistry, whereas other isoprenoids have diverse roles ranging from various biological processes to applications in commercial uses. Understanding the metabolic regulation of the MEP pathway is important considering the numerous applications of this pathway. The 1-deoxy-D-xylulose-5-phosphate synthase (DXS) enzyme was cloned from Populus trichocarpa, and the recombinant protein (PtDXS) was purified from Escherichia coli. The steady-state kinetic parameters were measured by a coupled enzyme assay. An LC-MS/MS-based assay involving the direct quantification of the end product of the enzymatic reaction, 1-deoxy-D-xylulose 5-phosphate (DXP), was developed. The effect of different metabolites of the MEP pathway on PtDXS activity was tested. PtDXS was inhibited by IDP and DMADP. Both of these metabolites compete with thiamine pyrophosphate for binding with the enzyme. An atomic structural model of PtDXS in complex with thiamine pyrophosphate and Mg(2+) was built by homology modeling and refined by molecular dynamics simulations. The refined structure was used to model the binding of IDP and DMADP and indicated that IDP and DMADP might bind with the enzyme in a manner very similar to the binding of thiamine pyrophosphate. The feedback inhibition of PtDXS by IDP and DMADP constitutes an important mechanism of metabolic regulation of the MEP pathway and indicates that thiamine pyrophosphate-dependent enzymes may often be affected by IDP and DMADP.
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