Perturbations in Histidine Biosynthesis Uncover Robustness in the Metabolic Network of Salmonella enterica 英文参考文献.docVIP

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Perturbations in Histidine Biosynthesis Uncover Robustness in the Metabolic Network of Salmonella enterica 英文参考文献.doc

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Perturbations in Histidine Biosynthesis Uncover Robustness in the Metabolic Network of Salmonella enterica 英文参考文献

PerturbationsinHistidineBiosynthesisUncover RobustnessintheMetabolicNetworkofSalmonella enterica MarkJ.Koenigsknecht¤,JenniferA.Lambrecht,LukeA.Fenlon,DianaM.Downs* DepartmentofBacteriology,UniversityofWisconsin-Madison,Madison,Wisconsin,UnitedStatesofAmerica Abstract Phosphoribosylamine (PRA) is an intermediate in the biosynthetic pathway that is common to thiamine and purines. Glutaminephosphoribosylpyrophosphate(PRPP)amidotransferaseistheproductofthepurFgeneinSalmonellaenterica andcatalyzesthesynthesisofPRAfromPRPPandglutamine.StrainslackingPurFrequireexogenousadditionofpurinesfor growth.However,undersomegrowthconditionsorwithspecificsecondarymutationsthesestrainsgrowintheabsenceof exogenous thiamine. Mutant alleles of hisA, which encodes 1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino) methylide- neamino]imidazole-4-carboxamide(ProFAR)isomerase,allowedPurF-independentPRAformation.TheallelesofhisAthat suppressedtherequirementforexogenousthiamineresultedinproteinswithreducedenzymaticactivity.Datapresented hereshowed thatdecreased activityofHisA altered metabolitepools andallowedPRA formation fromProFAR.Possible mechanismsofthisconversionwereproposed.Theresultshereinemphasizetheplasticityofthemetabolicnetworkand specificallyhighlightthepotentialforchemicalsynthesestocontributetonetworkrobustness. Citation:KoenigsknechtMJ,LambrechtJA,FenlonLA,DownsDM(2012)PerturbationsinHistidineBiosynthesisUncoverRobustnessintheMetabolicNetworkof Salmonellaenterica.PLoSONE7(10):e48207.doi:10.1371/journal.pone.0048207 Editor:ValeriedeCre′cy-Lagard,UniversityofFlorida,UnitedStatesofAmerica ReceivedAugust6,2012;AcceptedSeptember25,2012;PublishedOctober25,2012 Copyright:?2012Koenigsknechtetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by competitive grant GM47296 from the National Institutes