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Integrating Kinetic Model of E. coli with Genome Scale Metabolic Fluxes Overcomes Its Open System Problem and Reveals Bistability in Central Metabolism

Mannan, AA, Toya, T, Shimizu, K, McFadden, J, Kierzek, AM and Rocco, A (2015) Integrating Kinetic Model of E. coli with Genome Scale Metabolic Fluxes Overcomes Its Open System Problem and Reveals Bistability in Central Metabolism PLoS One, 10 (10), e01395.

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Abstract

An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, limiting the size of the system that can be modelled. Furthermore, the subsystem of the metabolic network whose dynamics can be modelled is faced with three problems: how to parameterize the model with mostly incomplete steady state data, how to close what is now an inherently open system, and how to account for the impact on growth. In this study we address these challenges of kinetic modelling by capitalizing on multi-‘omics’ steady state data and a genome-scale metabolic network model. We use these to generate parameters that integrate knowledge embedded in the genome-scale metabolic network model, into the most comprehensive kinetic model of the central carbon metabolism of E. coli realized to date. As an application, we performed a dynamical systems analysis of the resulting enriched model. This revealed bistability of the central carbon metabolism and thus its potential to express two distinct metabolic states. Furthermore, since our model-informing technique ensures both stable states are constrained by the same thermodynamically feasible steady state growth rate, the ensuing bistability represents a temporal coexistence of the two states, and by extension, reveals the emergence of a phenotypically heterogeneous population.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Microbial and Cellular Sciences
Authors :
AuthorsEmailORCID
Mannan, AAUNSPECIFIEDUNSPECIFIED
Toya, TUNSPECIFIEDUNSPECIFIED
Shimizu, KUNSPECIFIEDUNSPECIFIED
McFadden, JUNSPECIFIEDUNSPECIFIED
Kierzek, AMUNSPECIFIEDUNSPECIFIED
Rocco, AUNSPECIFIEDUNSPECIFIED
Date : 15 October 2015
Identification Number : 10.1371/journal.pone.0139507
Additional Information : Copyright: © 2015 Mannan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Depositing User : Symplectic Elements
Date Deposited : 11 Nov 2015 12:37
Last Modified : 11 Nov 2015 12:37
URI: http://epubs.surrey.ac.uk/id/eprint/809230

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