Genome-scale modeling using flux ratio constraints to enable metabolic engineering of clostridial metabolism in silico.

BMC Systems Biology
Michael J McAnultyRyan S Senger

Abstract

Genome-scale metabolic networks and flux models are an effective platform for linking an organism genotype to its phenotype. However, few modeling approaches offer predictive capabilities to evaluate potential metabolic engineering strategies in silico. A new method called "flux balance analysis with flux ratios (FBrAtio)" was developed in this research and applied to a new genome-scale model of Clostridium acetobutylicum ATCC 824 (iCAC490) that contains 707 metabolites and 794 reactions. FBrAtio was used to model wild-type metabolism and metabolically engineered strains of C. acetobutylicum where only flux ratio constraints and thermodynamic reversibility of reactions were required. The FBrAtio approach allowed solutions to be found through standard linear programming. Five flux ratio constraints were required to achieve a qualitative picture of wild-type metabolism for C. acetobutylicum for the production of: (i) acetate, (ii) lactate, (iii) butyrate, (iv) acetone, (v) butanol, (vi) ethanol, (vii) CO2 and (viii) H2. Results of this simulation study coincide with published experimental results and show the knockdown of the acetoacetyl-CoA transferase increases butanol to acetone selectivity, while the simultaneous over-express...Continue Reading

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Apr 17, 2013·BMC Systems Biology·S Alexander RiemerDietmar Schomburg
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Methods Mentioned

BETA
gene knockouts
gene
gene knockout

Software Mentioned

GLPK
COBRA
CoAT
OptKnock
METAFoR
FBrAtio
OptForce

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