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  4. Systematic characterization of flux and network thermodynamic states for identification of metabolic engineering targets
 
conference poster not in proceedings

Systematic characterization of flux and network thermodynamic states for identification of metabolic engineering targets

Soh, Keng Cher  
•
Miskovic, Ljubisa  
•
Hatzimanikatis, Vassily  
2012
Metabolic Engineering IX

In order to identify targets for metabolic engineering interventions or understand the physiology of the cell, the first and foremost prerequisite is the knowledge or a hypothesis about the intracellular network state(s). However, even with the advanced metabolomics and fluxomics methods currently at our disposal, it is still impossible or rather difficult to determine the exact intracellular flux states due to the number of reactions in the real system compounded with the reversibility of many of these reactions. As such, it may not be feasible to elucidate exactly the single state of the cell but to propose what could be all the possible states under given fermentation conditions, and ask what are the most important and consistent factors for achieving our metabolic engineering target given these states. In this contribution, we developed a framework for identifying all the possible intracellular flux and thermodynamic states using available experimental information provided, such as substrates/products profiles and any additional information such as metabolite concentrations and regulatory constraints that can be systematically integrated to differentiate all the possible directional profiles. Using the methods from Thermodynamics-based Flux Balance Analysis (TFBA), we then perform sampling of the flux and metabolite concentration states, which ensures network thermodynamic consistency, and we employ statistical techniques in order to extract representative flux and concentration profiles for the different network states. With these representative flux and concentration states, we can next perform kinetic analysis in order to identify targets for metabolic engineering and select those that are consistently important across these possible states.

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

2012

Subjects

thermodynamics

•

Metabolic control analysis

•

metabolic flux analysis

•

metabolic engineering

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/20.500.14299/81481
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