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1、EnvironmentsthatInduceSyntheticMicrobialEcosystems11,2NielsKlitgord,DanielSegre`*1BioinformaticsProgram,BostonUniversity,Boston,Massachusetts,UnitedStatesofAmerica,2DepartmentofBiologyandDepartmentofBiomedicalEngineering,BostonUniversity,Boston,Massachusetts,UnitedStatesofAmericaAbstr
2、actInteractionsbetweenmicrobialspeciesaresometimesmediatedbytheexchangeofsmallmolecules,secretedbyonespeciesandmetabolizedbyanother.Bothone-way(commensal)andtwo-way(mutualistic)interactionsmaycontributetocomplexnetworksofinterdependencies.Understandingtheseinteractionsconstitutesanope
3、nchallengeinmicrobialecology,withapplicationsrangingfromthehumanmicrobiometoenvironmentalsustainability.Inparalleltonaturalcommunities,itispossibletoexploreinteractionsinartificialmicrobialecosystems,e.g.pairsofgeneticallyengineeredmutualisticstrains.Herewecomputationallygenerateartif
4、icialmicrobialecosystemswithoutre-engineeringthemicrobesthemselves,butratherbypredictingtheirgrowthonappropriatelydesignedmedia.Weusegenome-scalestoichiometricmodelsofmetabolismtoidentifymediathatcansustaingrowthforapairofspecies,butfailtodosoforoneorbothindividualspecies,therebyinduc
5、ingputativesymbioticinteractions.Wefirsttestedourapproachontwopreviouslystudiedmutualisticpairs,andonapairofhighlycuratedmodelorganisms,showingthatouralgorithmssuccessfullyrecapitulateknowninteractions,robustlypredictnewones,andprovidenovelinsightonexchangedmolecules.Wethenappliedourm
6、ethodtoallpossiblepairsofsevenmicrobialspecies,andfoundthatitisalwayspossibletoidentifyputativemediathatinducecommensalismormutualism.Ouranalysisalsosuggeststhatsymbioticinteractionsmayarisemorereadilythroughenvironmentalfluctuationsthangeneticmodifications.Weenvisionthatourapproachwi
7、llhelpgeneratemicrobe-microbeinteractionmapsusefulforunderstandingmicrobialconsortiadynamicsandevolution,andforexploringthefullpotentialofnaturalmetabolicpathwaysformetabolicengineeringapplications.Citation:KlitgordN,Segre`D(2010)EnvironmentsthatInduceSyntheticMicrobialEcosystems.PLoS
8、Compu