K.Brinkrolfetal./JournalofBiotechnology149 (2010) 173–182

Table1(Continued)Codingregioncg1846cg1861cg1935cg2102

Alternativeidenti erNCgl1578NCgl1590NCgl1650NCgl1844

Genename–relgntR2sigB

ProteinfamilyTetR–

GntR

Sigmafactor

Numberoftargetgenesa

471017

EvidencebEPEE

Regulatoryroleandphysiologicalfunctionoftranscriptionregulatorc

177

cg2103cg2112cg2114cg2115cg2118cg2152cg2268cg2309cg2500cg2502cg2516cg2615cg2624cg2783cg2831cg2888cg2894cg2942cg2965cg3082cg3097cg3202cg3224cg3239cg3253cg3352cg3388cg3420

abc

NCgl1845NCgl1853NCgl1855NCgl1856NCgl1859NCgl1887NCgl1989NCgl2025NCgl2199NCgl2200NCgl2211NCgl2299NCgl2308NCgl2440NCgl2472NCgl2518NCgl2523NCgl2567NCgl2587NCgl2584NCgl2699NCgl2794NCgl2814NCgl2827NCgl2840NCgl2921NCgl2954NCgl2983

dtxRnrdRlexAsugRfruRclgR–bioQznrzurhrcAvanRpcaRgntR1ramAphoR––––hspRfarRlldR–mcbRnagR–sigM

DtxRNrdRLexADeoRDeoRHTH3LysRTetRArsRFurHrcAPadRIclRGntRLuxR

ResponseregulatorTetRAsnCAraCArsRMerRGntRGntRLysRTetRIclRIclR

Sigmafactor

64348405816294312102418211471061465317

EPEEEEPPEEEEEEEEEPPEEEEPEEPE

Repressorofcg1845-cg1844genesandcg1847(p)ppGppsynthetaseinvolvedinsigmafactorcompetition

DualregulatorinvolvedincarbonmetabolismGroup2sigmafactor(masterregulator)

involvedingeneexpressionduringtransitionphaseandunderoxygendeprivationDualregulator(masterregulator)ofironmetabolism

RepressorofribonucleotidereductasegenesnrdHIE

Dualregulator(masterregulator)ofSOSresponse

Repressor(masterregulator)involvedincarbonmetabolism

RepressoroffructosePTSsystemgenes

ActivatorofproteolysisandDNArepairgenesActivatorofmembraneproteingenecg2269Repressorofbiotinuptakeandbiosynthesisgenes

RepressoroftranscriptionregulatorgenezurRepressorofzincuptakesystemgenes

RepressorofheatshockresponsegeneswithCIRCEelements

RepressorofvanillatemetabolismgenesvanABK

RepressorofprotocatechuatemetabolismgenesDualregulatorinvolvedincarbonmetabolismDualregulator(masterregulator)ofcarbonmetabolism

Activator(masterregulator)ofphosphatemetabolism

RepressorofMFS-typetransportergenecg2893ActivatorofLysE-typetranslocatorgenecg2941Activatorofphenoldegradationgenecg2966Repressorofcg3083–cg3085genes

RepressorofheatshockresponsegeneswithHAIRelements

Repressorofarginineandglutamatebiosynthesisgenes

Repressorinvolvedincarbonmetabolism

ActivatorofMFS-typetransportergenecg3240Repressor(masterregulator)ofsulfurmetabolism

Activatorofgentisateuptakeanddegradationgenes

Activatorofhydroxyquinolpathwaygenescg3387–cg3385

ECFsigmafactorinvolvedinexpressionofoxidativestressresponsegenes

CurrentnumberoftargetgenesstoredinCoryneRegNet5.0(July2009).Abbreviations:E,experimentalevidence;P,computationalprediction.

ReferencesforcorrespondingoriginalarticlesareavailablefromtheliteraturesectioninCoryneRegNet.

2.3.CurrentstatusoftranscriptionalregulatorynetworkreconstructioninC.glutamicum

RecentregulatorynetworkreconstructionswithGraphVisandtheentiredatasetofregulatoryinteractionsstoredinCoryneReg-Netincluded544genes,i.e.around20%ofthepredictednumberofC.glutamicumATCC13032genes(KohlandTauch,2009).Thesenetworkreconstructionsrevealedacross-linkageofregulatoryunitstoacomplexnetworkstructure,aso-calledmotifsuper-cluster(Dobrinetal.,2004),including92%ofthehithertoknownregulatoryinteractionsinC.glutamicum.Moreover,amodulararchitectureoftheregulatorynetworkwasobserved,showingsixconnectedunitswithwell-de nedphysiologicalfunctions,includ-ing(i)carbonmetabolism,(ii)sulfurandironhomeostasis,(iii)SOSandstressresponse,(iv)respiration,(v)nitrogenmetabolism,and(vi)phosphatemetabolism.Asexpected,eachofthesefunctionalmoduleswascharacterizedbythepresenceofmasterregulators,suchasMcbR,DtxR,LexA,SigH,ArnR,AmtR,andPhoR,sensingdistinctenvironmentalinputstocontroltheexpressionoffunction-allyrelatedtargetgeneswithintheircorrespondingmodules.ThehierarchicalstructureoftheregulatorynetworkofC.glutamicumwasalsoevidentfromthereconstruction,sincelocalregulatorsweredetectedwithinfunctionalmodules,eitheraspartofthesuperclusterorasseparatemotifswithcorrespondingphysiolog-icalfunctions(Kohletal.,2008).Theonlyregulatoryhub(globalregulatorynetworknode)currentlyknownintheTRNofC.glu-tamicumisGlxR.Recentcomputationalpredictionswithare nedpositionweightmatrixindicatedthatGlxRmightbeinvolvedindirectlycontrollingaround14%oftheentiregenesetofC.glutam-icumATCC13032(KohlandTauch,2009).Thissetincludes23genesfortranscriptionregulators,suggestingthatahighnumberofC.glu-tamicumgenesareunderhierarchicalcontrolbyGlxR,asithasbeenobservedforthehomologousregulatorCRPinE.coli(MadanBabuandTeichmann,2003).