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  4. Metabolic control analysis of the central carbon pathway in optimally grown E. coli
 
conference poster not in proceedings

Metabolic control analysis of the central carbon pathway in optimally grown E. coli

Andreozzi, Stefano  
•
Miskovic, Ljubisa  
•
Soh, Keng Cher  
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2012
Metabolic Engineering IX

The engineering of the metabolism requires the building of reliable kinetic models of the metabolic pathways through the integration of the information from heterogeneous data sources. Unfortunately, the quantitative knowledge about fluxes, mechanisms or kinetic parameters of the constituent reactions of the metabolic network is most of the times uncertain or missing, due to limitations in the measurement techniques of the relevant biological properties of the cell and variability in experimental conditions. In this contribution, we employ ORACLE (Optimization and Risk Analysis of Complex Living Entities), the computational framework for the analysis and optimization of metabolic networks that addresses these issues. ORACLE allows us to generate populations of kinetic models that account explicitly for the physico-chemical and thermodynamic features and constraints of metabolic networks. We show how ORACLE incorporates fluxomics and metabolomics data and constraints into the central carbon core model of E. coli to uncover its possible steady state behaviors, when the cells are cultivated under the physiological condition of optimal growth on different carbon sources, both anaerobically and aerobically. Alternative cases of possible intracellular flux and thermodynamic states, corresponding to the given experimental data, are identified and subsequently the kinetic analysis is performed to evaluate how the control over fluxes and concentrations is distributed over the metabolic network. We demonstrate that ORACLE methodology provides guidance for metabolic engineering in spite of uncertain/missing information in the local/global properties of the metabolic network, integrating a statistical account on the semi-quantitative available data with consistent thermodynamic information and plausible hypotheses.

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Type
conference poster not in proceedings
Author(s)
Andreozzi, Stefano  
Miskovic, Ljubisa  
Soh, Keng Cher  
Hatzimanikatis, Vassily  
Date Issued

2012

Subjects

Metabolic engineering

•

Metabolic control analysis

•

optimal growth

•

sampling

•

uncertainty

Written at

EPFL

EPFL units
LCSB  
Event nameEvent placeEvent date
Metabolic Engineering IX

Biarritz, France

June 03-07, 2012

Available on Infoscience
June 11, 2012
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/81480
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