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

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dc.contributor.author McAnulty, Michael J
dc.contributor.author Yen, Jiun Y
dc.contributor.author Freedman, Benjamin G
dc.contributor.author Senger, Ryan S
dc.date.accessioned 2012-11-12T20:03:18Z
dc.date.available 2012-11-12T20:03:18Z
dc.date.issued 2012-05-14
dc.identifier.citation BMC Systems Biology. 2012 May 14;6(1):42
dc.identifier.uri http://dx.doi.org/10.1186/1752-0509-6-42
dc.identifier.uri http://hdl.handle.net/10919/19069
dc.description.abstract Abstract Background 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. Results 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-expression of the aldehyde/alcohol dehydrogenase greatly increases ethanol production. Conclusions FBrAtio is a promising new method for constraining genome-scale models using internal flux ratios. The method was effective for modeling wild-type and engineered strains of C. acetobutylicum.
dc.title Genome-scale modeling using flux ratio constraints to enable metabolic engineering of clostridial metabolism in silico
dc.type Journal Article
dc.date.updated 2012-11-12T20:03:19Z
dc.description.version Peer Reviewed
dc.language.rfc3066 en
dc.rights.holder Michael J McAnulty et al.; licensee BioMed Central Ltd.


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  • BioMed Central [323]
    BioMed Central publications by Virginia Tech authors.

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