FastPros: screening of reaction knockout strategies for metabolic engineering.

Abstract

Although constraint-based flux analysis of knockout strains has facilitated the production of desirable metabolites in microbes, current screening methods have placed a limitation on the number knockouts that can be simultaneously analyzed. Here, we propose a novel screening method named FastPros. In this method, the potential of a given reaction knockout for production of a specific metabolite is evaluated by shadow pricing of the constraint in the flux balance analysis, which generates a screening score to obtain candidate knockout sets. To evaluate the performance of FastPros, we screened knockout sets to produce each metabolite in the entire Escherichia coli metabolic network. We found that 75% of these metabolites could be produced under biomass maximization conditions by adding up to 25 reaction knockouts. Furthermore, we demonstrated that using FastPros in tandem with another screening method, OptKnock, could further improve target metabolite productivity. Source code is freely available at http://www-shimizu.ist.osaka-u.ac.jp/shimizu_lab/FastPros/, implemented in MATLAB and COBRA toolbox.