439775 OptStoic: Designing overall stoichiometric conversions and intervening reactions
439775 OptStoic: Designing overall stoichiometric conversions and intervening reactions
Friday, September 18, 2015: 11:30 AM
Crowne Plaza Heidelberg City Centre
Advances in synthetic biology tools have ushered a new era in the assembly and expression of non-native pathways in production hosts for the conversion of feedstock substrates to biofuel and biorenewable products. Existing computational tools for the de novo pathway assembly, either based on mixed integer linear programming techniques or graph-search applications, generally only find linear pathways connecting the source to the target metabolite. The overall stoichiometry of conversion along with alternate co-reactant (or co-product) combinations is not part of the pathway design. Therefore, global carbon and energy efficiency is in essence fixed with no opportunities to identify more efficient routes for recycling carbon flux or redox equivalents closer to the thermodynamic limit. Here, we introduce a two-stage procedure that both identifies the optimum overall stoichiometry and selects for (non-)native reactions that maximize carbon or energy efficiency while satisfying thermodynamic feasibility requirements. Implementation for recent pathway design studies identified non-intuitive pathway designs with improved efficiencies. Specifically, multiple alternatives for non-oxidative glycolysis are generated and non-intuitive ways of co-utilizing carbon dioxide with methanol are revealed for the production of 1-butanol with higher carbon efficiency. Likewise, several non-intuitive solutions were identified for driving forward the thermodynamically unfavorable conversion of methane to acetate and other C2+ metabolites.