title: Designing minimal microbial strains of desired functionality using a genetic algorithm.
abstract: 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.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Govind
authors.initials: G
authors.lastname: Nair
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Jungreuthmayer
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanscho
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria ; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zanghellini
keywords: Elementary flux modes; Metabolic networks; Minimal cut sets; Strain optimization; Systems biology