ArticlePloS one2012
Metabolite profiling identified methylerythritol cyclodiphosphate efflux as a limiting step in microbial isoprenoid production.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 105 citations in OpenAlex.
- Strategic selection of microbial cell factories for sustainable and application-specific terpenoid production.Frontiers in bioengineering and biotechnology · 2026Review
- Promiscuity of an Alcohol-Dependent Hemiterpene Pathway for the In Vivo Production of a Non-Natural Alkylated Tryptophan Derivative.ACS synthetic 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
- Systematic metabolic engineering ofFrontiers in bioengineering and biotechnology · 2024Article
- Evolutionary flexibility and rigidity in the bacterial methylerythritol phosphate (MEP) pathway.Frontiers in microbiology · 2023Article
- Production of Coenzyme QWorld journal of microbiology & biotechnology · 2022Review
- Adaptive evolution of Methylotuvimicrobium alcaliphilum to grow in the presence of rhamnolipids improves fatty acid and rhamnolipid production from CH4.Journal of industrial microbiology & biotechnology · 2022Article
- Multiscale engineering of microbial cell factories: A step forward towards sustainable natural products industry.Synthetic and systems biotechnology · 2022Review
- Alternative metabolic pathways and strategies to high-titre terpenoid production inNatural product reports · 2022Review
- Reprogramming microbial populations using a programmed lysis system to improve chemical production.Nature communications · 2021Article
- Advances in engineering microbial biosynthesis of aromatic compounds and related compounds.Bioresources and bioprocessing · 2021Review
- Establishment of strigolactone-producing bacterium-yeast consortium.Science advances · 2021Article
- Modular engineering for microbial production of carotenoids.Metabolic engineering communications · 2020Review
- Effect of Drought on the Methylerythritol 4-Phosphate (MEP) Pathway in the Isoprene Emitting ConiferFrontiers in plant science · 2020Article
- Advances in the development and application of microbial consortia for metabolic engineering.Metabolic engineering communications · 2019Review
- Investigation of the methylerythritol 4-phosphate pathway for microbial terpenoid production through metabolic control analysis.Microbial cell factories · 2019Article
- Engineering microbial consortia by division of labor.Microbial cell factories · 2019Review
- Two-step pathway for isoprenoid synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Metabolic engineering for the production of isoprene and isopentenol by Escherichia coli.Applied microbiology and biotechnology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isoprenoids are natural products that are all derived from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). These precursors are synthesized either by the mevalonate (MVA) pathway or the 1-Deoxy-D-Xylulose 5-Phosphate (DXP) pathway. Metabolic engineering of microbes has enabled overproduction of various isoprenoid products from the DXP pathway including lycopene, artemisinic acid, taxadiene and levopimaradiene. To date, there is no method to accurately measure all the DXP metabolic intermediates simultaneously so as to enable the identification of potential flux limiting steps. In this study, a solid phase extraction coupled with ultra performance liquid chromatography mass spectrometry (SPE UPLC-MS) method was developed. This method was used to measure the DXP intermediates in genetically engineered E. coli. Unexpectedly, methylerythritol cyclodiphosphate (MEC) was found to efflux when certain enzymes of the pathway were over-expressed, demonstrating the existence of a novel competing pathway branch in the DXP metabolism. Guided by these findings, ispG was overexpressed and was found to effectively reduce the efflux of MEC inside the cells, resulting in a significant increase in downstream isoprenoid production. This study demonstrated the necessity to quantify metabolites enabling the identification of a hitherto unrecognized pathway and provided useful insights into rational design in metabolic engineering.
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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.