Journal
METABOLIC ENGINEERING
Volume 13, Issue 2, Pages 204-213Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2010.12.004
Keywords
Metabolic engineering; Elementary modes; Minimal cut sets; Targeted modification; Strain optimization; Ethanol production
Categories
Funding
- German Federal Ministry of Education and Research (FORSYS center MaCS (Magdeburg Center for Systems Biology))
- Ministry of Education and Research of Saxony-Anhalt (Research Center Dynamic Systems)
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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 induceside 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. (C) 2010 Elsevier Inc. All rights reserved.
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