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Computing complex metabolic intervention strategies using constrained minimal cut sets

Paper ID Volume ID Publish Year Pages File Format Full-Text
31749 44835 2011 10 PDF Available
Title
Computing complex metabolic intervention strategies using constrained minimal cut sets
Abstract

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.

Keywords
Metabolic engineering; Elementary modes; Minimal cut sets; Targeted modification; Strain optimization; Ethanol productioncMCS(s), constrained minimal cut set(s); EM(s), elementary mode(s); EMA, elementary-mode analysis; FBA, flux balance analysis; MCS(s),
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 13, Issue 2, March 2011, Pages 204–213
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us