Predictive Potential of Flux Balance Analysis of Saccharomyces cerevisiae Using as Optimization Function Combinations of Cell Compartmental Objectives 英文参考文献.docVIP

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Predictive Potential of Flux Balance Analysis of Saccharomyces cerevisiae Using as Optimization Function Combinations of Cell Compartmental Objectives 英文参考文献.doc

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Predictive Potential of Flux Balance Analysis of Saccharomyces cerevisiae Using as Optimization Function Combinations of Cell Compartmental Objectives 英文参考文献

PredictivePotentialofFluxBalanceAnalysisof SaccharomycescerevisiaeUsingasOptimization FunctionCombinationsofCellCompartmental Objectives CarlosEduardoGarc?′aSa′nchez1*,Ce′sarAugustoVargasGarc?′a2,RodrigoGonzaloTorresSa′ez3 1Escuela de Ingenier?′a Qu?′mica, Grupo de Investigacio′n en Bioqu?′mica y Microbiolog?′a, Universidad Industrial de Santander, Bucaramanga, Santander, Colombia, 2Escuela de Ingenier?′a de Sistemas e Informa′tica, Grupo de Investigacio′n en Ingenier?′a Biome′dica, Universidad Industrial de Santander, Bucaramanga, Santander, Colombia,3EscueladeQu?′mica,GrupodeInvestigacio′nenBioqu?′micayMicrobiolog?′a,UniversidadIndustrialdeSantander,Bucaramanga,Santander,Colombia Abstract Background:Themainobjectiveoffluxbalanceanalysis(FBA)istoobtainquantitativepredictionsofmetabolicfluxesofan organism,anditisnecessarytouseanappropriateobjectivefunctiontoguaranteeagoodestimationofthosefluxes. Methodology:Inthisstudy,thepredictiveperformanceofFBAwasevaluated,usingobjectivefunctionsarisingfromthe linear combination of different cellular objectives. This approach is most suitable for eukaryotic cells, owing to their multiplicity of cellular compartments. For this reason, Saccharomyces cerevisiae was used as model organism, and its metabolicnetworkwasrepresentedusingthegenome-scalemetabolicmodeliMM904.Astheobjectivewastoevaluatethe predictive performance from the FBA using the kind of objective function previously described, substrate uptake and oxygen consumption were the only input data used for the FBA. Experimental information about microbial growth and exchangeofmetaboliteswiththeenvironmentwasusedtoassessthequalityofthepredictions. Conclusions:ThequalityofthepredictionsobtainedwiththeFBAdependsgreatlyontheknowledgeoftheoxygenuptake rate.Forthemostofstudiedclassifications,thebestpredictionswereobtainedwith‘‘maximizationofgrowth’’,andwith some combinations that include this objective. However, in the case of exponential growth with unknown oxygen exchange flux, t