Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine

Dalwadi, Mohit P. and King, John R. and Minton, Nigel P. (2017) Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine. Journal of Mathematical Biology . ISSN 1432-1416 (In Press)

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Abstract

A biosustainable production route for 3-hydroxypropionic acid (3HP), an important platform chemical, would allow 3HP to be produced without using fossil fuels. We are interested in investigating a potential biochemical route to 3HP from pyruvate through b -alanine and, in this paper, we develop and solve a mathematical model for the reaction kinetics of the metabolites involved in this pathway. We consider two limiting cases, one where the levels of pyruvate are never replenished, the other where the levels of pyruvate are continuously replenished and thus kept constant. We exploit the natural separation of both the time scales and the metabolite concentrations to make significant asymptotic progress in understanding the system without resorting to computationally expensive parameter sweeps. Using our asymptotic results, we are able to predict the most important reactions to maximize the production of 3HP in this system while reducing the maximum amount of the toxic intermediate compound malonic semialdehyde present at any one time, and thus we are able to recommend which enzymes experimentalists should focus on manipulating.

Item Type: Article
Keywords: Asymptotic analysis; Reaction kinetics; Synthetic biology; Metabolic pathways
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
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Depositing User: Eprints, Support
Date Deposited: 23 Oct 2017 11:39
Last Modified: 15 Nov 2017 15:59
URI: http://eprints.nottingham.ac.uk/id/eprint/47460

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