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Applying asymptotic methods to synthetic biology: modelling the reaction kinetics of the mevalonate pathway

Dalwadi, Mohit P.; Garavaglia, Marco; Webb, Joseph P.; King, John R.; Minton, Nigel P.


Mohit P. Dalwadi

Joseph P. Webb

Professor of Theoretical Mechanics

Professor of Applied Molecular Microbiology


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.


Dalwadi, M. P., Garavaglia, M., Webb, J. P., King, J. R., & Minton, N. P. (2018). Applying asymptotic methods to synthetic biology: modelling the reaction kinetics of the mevalonate pathway. Journal of Theoretical Biology, 439,

Journal Article Type Article
Acceptance Date Nov 28, 2017
Online Publication Date Dec 2, 2017
Publication Date Feb 14, 2018
Deposit Date Dec 1, 2017
Publicly Available Date Dec 2, 2017
Journal Journal of Theoretical Biology
Print ISSN 0022-5193
Electronic ISSN 1095-8541
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 439
Keywords asymptotic analysis; metabolic pathways; isoprenoid production
Public URL
Publisher URL


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