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.

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: https://nottingham-repository.worktribe.com/output/895831
• Publisher URL: https://link.springer.com/article/10.1007%2Fs00285-017-1189-3
• Contract Date: Oct 23, 2017