代谢网络通量和结构分析
——。查垄蓬羔杰妻堡生堂燕篓兰
Network—basedMetabolicFluxandStructureAnalysis
Abstract
lthasbeenrecognizedthatthebiologicfunctionisnotoillyinvolved濂asinglemetabolitebutalsothemultipleinteractionofmanymetabolites.Therefore,asystemviewpointshouldbetakenaccounttoanalyzethebiologiea}network。Nowadays,thou曲thetopologicalstructuresofthecentralmetabolicnetwo矗Sofcertainorganismhavebeenclarified.titeirmetaboliefluxdistributionsremainunclear.Moreover,solneresearchesshouldbetakenintodeepinvestigationespeciallyonthegene-knockoutmutant+ThatthefluxdistributionsoflargescalemetabolicnetworkhavebeenanalyzedbyvailOUStargetfunctionsisalSOourconcern,sincewhichmaycause{nconsistentresults.Anotherpurposeof也isworkist0illustratetherelationshipbetweengenotypeandphenotypeinthecom4,lexcellularneYgvorkofsaccharomycescerevisiae.Themainresultsaresunamarizedasfollows:
onl强eE。collcentralcarbonmetabolicnetworkisstudledfirstly,Based
ofFInxBalanteAnalysis(FBA)andMinimization
modelswereconstructedtocomputeMetabolicAdjustment(MOMA),somemathematicalthecarbondistributionsinthegene.knockoutmutant
analysisshowsthatthe
ofmutanttometaboticnetwork.Comparedwiththeexperimentalresults,thenormalizedMoMAanalysisisI_easonablesolvethecarbondistribution
metabolicnetwork
2.As8strncture-orientedmethod、Elementaryfluxmode(EFM)analysishasobtained{ts
oftherobustnessofthecentralmetabolism,aswellaspopul蕊钾inanalysis
ofsome
deletionpheno£ypenetworkfunctionorganisms.However,thismethodhasnOtbeenwidelyusedinmodelingofgeneByenumeratingallthemetabolicpathways,the
thefunctionalfeaturesEFManalysispmsenmdhereinhasidentifiedandpredictedthegrowthphenotypeofthe
ofEFMS.cerevisiae,AscomparedwiththeFBA,the
FBAjnpredictionofgenedetetiOnperformanceanalysisWaSsuperiortophenotype,EFManalysishasbeendemonstratedas寰挂effectivetooltobridgethegapbetweenmetabolicnetwork
3;Control—effective
representingthefluxesofandgrowthphenotype.ofEFM.importance
OUrfCEF)aredetemfineddirect!yeachreactionfortheefficientandnofromthesetflexibleoperationsoftheentirenetwork.Toknowledge,theremayberelationshipsbetweenthemetabolicflux
distributionandthegenetranscriptionlevel,howevertheCEFanalysispresentedheremayexhibitareasonablecorrectionfunctionbetweenthepathwaystructureandtheexperimentaltranscriptiondata,
KeyWords:MetabolicNetwork;MetabolicPathwayAnalysistFluxBalanceAnalysis~Il