Computing complex metabolic intervention strategies using constrained minimal cut sets

The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set o...

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Veröffentlicht in:Metabolic engineering 2011-03, Vol.13 (2), p.204-213
Hauptverfasser: Hädicke, Oliver, Klamt, Steffen
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Klamt, Steffen
description The model-driven search for gene deletion strategies that increase the production performance of microorganisms is an essential part of metabolic engineering. One theoretical approach is based on Minimal Cut Sets (MCSs) which are minimal sets of knockouts disabling the operation of a specified set of target elementary modes. A limitation of the current approach is that MCSs can induce side effects disabling also desired functionalities. We, therefore, generalize MCSs to Constrained MCSs (cMCSs) allowing for the additional definition of a set of desired modes of which a minimum number must be preserved. Exemplarily for ethanol production by Escherichia coli, we demonstrate that this approach offers enormous flexibility in defining and solving knockout problems. Moreover, many existing methods can be reformulated as special cMCS problems. The cMCSs approach allows systematic enumeration of all equivalent gene deletion combinations and also helps to determine robust knockout strategies for coupled product and biomass synthesis.
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subjects Algorithms
Computer Simulation
Elementary modes
Escherichia coli
Escherichia coli - genetics
Escherichia coli - metabolism
Ethanol - metabolism
Ethanol production
Gene Deletion
Gene Knockout Techniques
Genetic Engineering
Metabolic engineering
Metabolic Networks and Pathways - genetics
Minimal cut sets
Models, Biological
Strain optimization
Targeted modification
title Computing complex metabolic intervention strategies using constrained minimal cut sets
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