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

Dalwadi, Mohit P.; King, John R.; Minton, Nigel P.

Authors

Mohit P. Dalwadi mohit.dalwadi@nottingham.ac.uk

JOHN KING john.king@nottingham.ac.uk
Professor of Theoretical Mechanics

NIGEL MINTON nigel.minton@nottingham.ac.uk
Professor of Appliedmolecular Microbiology



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.

Citation

Dalwadi, M. P., King, J. R., & Minton, N. P. (2018). 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, 77(1), 165-199. https://doi.org/10.1007/s00285-017-1189-3

Journal Article Type Article
Acceptance Date Oct 16, 2017
Online Publication Date Nov 20, 2017
Publication Date Jul 30, 2018
Deposit Date Oct 23, 2017
Publicly Available Date Nov 20, 2017
Journal Journal of Mathematical Biology
Print ISSN 0303-6812
Electronic ISSN 1432-1416
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 77
Issue 1
Pages 165-199
DOI https://doi.org/10.1007/s00285-017-1189-3
Keywords Asymptotic analysis; Reaction kinetics; Synthetic biology; Metabolic pathways
Public URL http://eprints.nottingham.ac.uk/id/eprint/47460
Publisher URL https://link.springer.com/article/10.1007%2Fs00285-017-1189-3
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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