Journal
ALGORITHMS FOR MOLECULAR BIOLOGY
Volume 10, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13015-015-0060-6
Keywords
Systems biology; Metabolic networks; Elementary flux modes; Minimal cut sets; Strain optimization
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Funding
- Federal Ministry of Science, Research and Economy (BMWFW)
- Federal Ministry of Traffic, Innovation and Technology (bmvit)
- Styrian Business Promotion Agency SFG
- Standortagentur Tirol and ZIT - Technology Agency of City of Vienna through COMET-Funding Program
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Background: The rational, in silico prediction of gene-knockouts to turn organisms into efficient cell factories is an essential and computationally challenging task in metabolic engineering. Elementary flux mode analysis in combination with constraint minimal cut sets is a particularly powerful method to identify optimal engineering targets, which will force an organism into the desired metabolic state. Given an engineering objective, it is theoretically possible, although computationally impractical, to find the best minimal intervention strategies. Results: We developed a genetic algorithm (GA-MCS) to quickly find many (near) optimal intervention strategies while overcoming the above mentioned computational burden. We tested our algorithm on Escherichia coli metabolic networks of three different sizes to find intervention strategies satisfying three different engineering objectives. Conclusions: We show that GA-MCS finds all practically relevant targets for any (non)-linear engineering objective. Our algorithm also found solutions comparable to previously published results. We show that for large networks optimal solutions are found within a fraction of the time used for a complete enumeration.
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