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New screening method greatly facilitates production of desirable metabolites in microbes

2013-11-29(Fri)

Under the leadership of SHIMIZU Hiroshi (Professor, Graduate School of Information Science, Osaka University) and FURUSAWA Chikara (Team Leader, Quantitative Biology Center, Riken), a group of researchers has developed a screening method named FastPros for obtaining optimal knockout sets in order to facilitate the production of desirable metabolites in microbes.
In the production of useful metabolites in microbes, it is necessary to artificially control the production quantity of metabolites and their properties through gene manipulation. However, due to the complexity of metabolic systems, it has been difficult to select the appropriate set of modifications from the enormous number of possible combinations in the production of desired compounds.
In order to overcome this problem, this group developed a new iterative screening algorithm called FastPros (Fast algorithm of knockout screening for target Production based on shadow price analysis) which uses biomass production maximization to identify sets of metabolic reactions whose simultaneous knockouts result in the production of a target metabolite.
In order to investigate the performance of FastPros, this group selected 625 metabolites in the E. coli metabolic model and screened reaction knockout sets. As a result, for 75 percent compounds including amino acid, plastic materials, drug materials, this group succeeded in obtaining a set of reaction knockouts resulting in an optimal yield of a target metabolite. This group's technique has achieved the design of appropriate metabolic networks making it possible to easily obtain the optimized metabolic network based on computer simulation. As FastPros screening method can be used for metabolic engineering for cell-wide metabolite production in cells, it will greatly increase the efficiency of valuable metabolite production in microbes.
Abstract

Motivation: While constraint-based flux analysis of knockout strainshas facilitated the production of desirable metabolites in microbes,current screening methods have placed a limitation on the number knockouts that can be simultaneously analyzed.
Results: Here, we propose a novel screening method namedFastPros. 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 theperformance of FastPros, we screened knockout sets to produce each metabolite in the entire Escherichia coli metabolic network. Wefound 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.

Metabolism

Figure 1

To learn more about this research, please read the full research report entitled "FastPros: screening of reaction knockout strategies for metabolic engineering" at this page of the Bioinformatics website.


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