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

Dalwadi, Mohit P. and Garavaglia, Marco and Webb, Joseph P. and King, John R. and Minton, Nigel P. (2018) Applying asymptotic methods to synthetic biology: modelling the reaction kinetics of the mevalonate pathway. Journal of Theoretical Biology, 439 . pp. 39-49. ISSN 1095-8541

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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.

Item Type: Article
Keywords: asymptotic analysis; metabolic pathways; isoprenoid production
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
University of Nottingham, UK > Faculty of Science > School of Mathematical Sciences
Identification Number: 10.1016/j.jtbi.2017.11.022
Depositing User: Eprints, Support
Date Deposited: 01 Dec 2017 11:51
Last Modified: 14 Dec 2017 11:49
URI: http://eprints.nottingham.ac.uk/id/eprint/48475

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