Modelling and Analysis of Central Metabolism Operating Regulatory Interactions in Salt Stress Conditions in a L-Carnitine Overproducing E. coli Strain 英文参考文献.docVIP

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Modelling and Analysis of Central Metabolism Operating Regulatory Interactions in Salt Stress Conditions in a L-Carnitine Overproducing E. coli Strain 英文参考文献.doc

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Modelling and Analysis of Central Metabolism Operating Regulatory Interactions in Salt Stress Conditions in a L-Carnitine Overproducing E. coli Strain 英文参考文献

ModellingandAnalysisofCentralMetabolismOperating RegulatoryInteractionsinSaltStressConditionsinaL- CarnitineOverproducingE.coliStrain GuidoSantos1,Jose′ A.Hormiga1,PaulaArense2,ManuelCa′novas2,Ne′storV.Torres1* 1DepartamentodeBioqu?′micayBiolog?′aMolecular,UniversidaddeLaLaguna,SanCristo′baldeLaLaguna,SantaCruzdeTenerife,Spain,2DepartamentodeBioqu?′mica yBiolog?′aMolecularB,UniversidaddeMurcia,Murcia,Spain Abstract BasedonexperimentaldatafromE.colicultures,wehavedevisedamathematicalmodelintheGMA-powerlawformalism thatdescribesthecentralandL-carnitinemetabolisminandbetweentwosteadystates,non-osmoticandhyperosmotic (0.3MNaCl).Akeyfeatureofthismodelistheintroductionoftypeofkineticorder,theosmoticstresskineticorders(gOSn ), derivedfromthepowerlawgeneralformalism,whichrepresenttheeffectofosmoticstressineachmetabolicprocessofthe model.ByconsideringthevaluesofthegOSnlinkedtoeachmetabolicprocesswefoundthatosmoticstresshasapositive anddeterminantinfluenceontheincreaseinfluxinenergeticmetabolism(glycolysis);L-carnitinebiosynthesisproduction; thetransformation/excretionofAcetyl-CoAintoacetateandethanol;theinputfluxofpeptoneintothecell;theanabolic useofpyruvateandbiomassdecomposition.Incontrast,wefoundthatalthoughtheosmoticstresshasaninhibitoryeffect on the transformation flux from the glycolytic end products (pyruvate) to Acetyl-CoA, this inhibition is counteracted by othereffects(theincreaseinpyruvateconcentration)totheextentthatthewholefluxincreases.Inthesamevein,thedown regulationexertedbyosmoticstressonfumarateuptakeanditsoxidationandtheproductionandexportoflactateand pyruvatearereversedbyotherfactorsuptothepointthatthefirstincreasedandthesecondremainedunchanged.The model analysis shows that in osmotic conditions the energy and fermentation pathways undergo substantial rearrangement. This is illustrated by the observation that the increase in the fermentation fluxes is not connected with fluxestowardsthetricaboxylicacidintermediatesandthesynthesisofbiomass.Theosmotics