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

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...

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Main Authors: Dalwadi, Mohit P., King, John R., Minton, Nigel P.
Format: Article
Published: Springer Verlag 2017
Subjects:
Online Access:https://eprints.nottingham.ac.uk/47460/
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author Dalwadi, Mohit P.
King, John R.
Minton, Nigel P.
author_facet Dalwadi, Mohit P.
King, John R.
Minton, Nigel P.
author_sort Dalwadi, Mohit P.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-474602020-05-04T19:18:53Z https://eprints.nottingham.ac.uk/47460/ 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. 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. Springer Verlag 2017-11-20 Article PeerReviewed Dalwadi, Mohit P., 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 Asymptotic analysis; Reaction kinetics; Synthetic biology; Metabolic pathways https://link.springer.com/article/10.1007%2Fs00285-017-1189-3 doi:10.1007/s00285-017-1189-3 doi:10.1007/s00285-017-1189-3
spellingShingle Asymptotic analysis; Reaction kinetics; Synthetic biology; Metabolic pathways
Dalwadi, Mohit P.
King, John R.
Minton, Nigel P.
Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
title Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
title_full Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
title_fullStr Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
title_full_unstemmed Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
title_short Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
title_sort multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine
topic Asymptotic analysis; Reaction kinetics; Synthetic biology; Metabolic pathways
url https://eprints.nottingham.ac.uk/47460/
https://eprints.nottingham.ac.uk/47460/
https://eprints.nottingham.ac.uk/47460/