ArticleJournal of theoretical biology2018
Applying asymptotic methods to synthetic biology: Modelling the reaction kinetics of the mevalonate pathway.
Article in Journal of theoretical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Complex Kinetic Models Predict β-Carotene Production and Reveal Flux Limitations in RecombinantACS synthetic biology · 2025Article
- Changing biosynthesis of terpenoid percursors in rice through synthetic biology.Frontiers in plant science · 2023Article
- Synthetic biology toolkit for engineering Cupriviadus necator H16 as a platform for COBiotechnology for biofuels · 2021Review
- Using singular perturbation theory to determine kinetic parameters in a non-standard coupled enzyme assay.Journal of mathematical biology · 2020Article
- An Asymptotic Analysis of the Malonyl-CoA Route to 3-Hydroxypropionic Acid in Genetically Engineered Microbes.Bulletin of mathematical biology · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The mevalonate pathway is normally found in eukaryotes, and allows for the production of isoprenoids, a useful class of organic compounds. This pathway has been successfully introduced to Escherichia coli, enabling a biosynthetic production route for many isoprenoids. In this paper, we develop and solve a mathematical model for the concentration of metabolites in the mevalonate pathway over time, accounting for the loss of acetyl-CoA to other metabolic pathways. Additionally, we successfully test our theoretical predictions experimentally by introducing part of the pathway into Cupriavidus necator. In our model, we exploit the natural separation of time scales as well as of metabolite concentrations to make significant asymptotic progress in understanding the system. We confirm that our asymptotic results agree well with numerical simulations, the former enabling us to predict the most important reactions to increase isopentenyl diphosphate production whilst minimizing the levels of HMG-CoA, which inhibits cell growth. Thus, our mathematical model allows us to recommend the upregulation of certain combinations of enzymes to improve production through the mevalonate pathway.
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Registered trials
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