In recent years, a growing number of strain design techniques have employed constraint-based modeling to determine metabolic network changes to improve chemical production. These methods use systems-level analysis of metabolism to guide experimental efforts by identifying deletions, additions, downregulations, and upregulations of metabolic genes that will increase biological production of a desired metabolic product. In this work, we propose a new strain design method (CosMos) that provides strategies for deletions, downregulations, and upregulations of metabolic genes that will lead to production of desired products and biofuels. The method is simple and easy to implement, and can provide additional strategies over current approaches. Using CosMos, we identified modification strategies for producing a variety of metabolic products, compared strategies derived from Escherichia coli and Saccharomyces cerevisiae metabolic models, and examined how imperfect implementation may affect experimental outcomes. This study gives a powerful and flexible technique for strain engineering.

Constraint-based strain design using continuous up and downregulation of fluxes

245th National Meeting (2013)

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