JournalofBiotechnology149 (2010) 173–182

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ThetranscriptionalregulatoryrepertoireofCorynebacteriumglutamicum:Reconstructionofthenetworkcontrollingpathwaysinvolvedinlysineandglutamateproduction

KarinaBrinkrolf,JasminSchröder,AlfredPühler,AndreasTauch

InstitutfürGenomforschungundSystembiologie,CentrumfürBiotechnologie,UniversitätBielefeld,Universitätsstraße27,D-33615Bielefeld,Germany

articleinfoabstract

CorynebacteriumglutamicumisoneofthebeststudiedorganismsofthehighG+CbranchofGram-positivebacteriaandanemergingmodelsystemforthesuborderCorynebacterineae.TogaininsightsintotheregulatorygenecompositionandarchitectureofthetranscriptionalregulatorynetworkofC.glutamicum,componentsofthetranscriptionalregulatoryrepertoirewereintensivelystudiedbymanyscienti cgroupsinrecentyears.Inthismini-review,wesummarizethepresentknowledgeaboutthededucedtranscriptionalregulatoryrepertoireofC.glutamicumandthecurrentstatusoftranscriptionalregulatorynetworkreconstructionwithregardtothegenome-widedetectionoftranscriptionalregula-tions,coregulatoryinteractionsandhierarchicalcross-regulations.Moreover,weprovideanoverviewofthoseregulatorsandtheirtranscriptionalregulationscontrollinggenesinvolvedintheconversionofthecarbonsourcesglucose,fructoseandsucroseintotheindustriallyrelevantproductsl-lysineandl-glutamate.Thisdatawillcontributetoourunderstandingofl-lysineandl-glutamateproductionbyC.glutamicumfromtheperspectiveofsystemsbiologyandmayprovidethebasisforcomputationalmodelingoftherespectivebiotechnologicallyimportantmetabolicpathways.

© 2009 Elsevier B.V. All rights reserved.

Articlehistory:

Received18August2009Receivedinrevisedform19November2009

Accepted1December2009

Keywords:

CorynebacteriumglutamicumTranscriptionregulation

TranscriptionalregulatorynetworkGlutamatebiosynthesisLysinebiosynthesisSystemsbiology

1.Introduction

Thetranscriptionalregulatorynetwork(TRN)ofbacteriaisafundamentalbiologicalsystemcontrollingthe owofinforma-tionfromtheinternalandexternalenvironmenttothegenelevelandthustospeci ccellularfunctions(Seshasayeeetal.,2006).Inconjunctionwithadiversemetabolism,theTRNenablesarapidadaptationofmicroorganismstochangingenvironmentalcon-ditions.ThemaincomponentsofaTRNareregulatoryproteinstermedtranscriptionregulatorsthatsensediversestimuliandrec-ognizeandbindtospeci cDNAsequences(operators)tocontrolandmodulatetheexpressionoftheirtargetgenes(MadanBabuandTeichmann,2003).Thisbasicgeneticprincipleallowstherecon-structionofthis owofinformationinformofadirectedgraph,whichiscommonlyreferredtoastheTRN(Babuetal.,2004).Insuchnetworks,nodesrepresenttranscriptionregulatorsandtheirtargetgenes,anddirectededgesrepresenttheregulatoryinter-actionbetweenthem.Accordingly,transcriptionregulatorsandtargetgenesformregulatoryunitscross-linkedtosimplenetworkmotifsthatarecharacteristictopologicalandfunctionalelements

Abbreviation:TRN,transcriptionalregulatorynetwork.

Correspondingauthor.Tel.:+495211068703;fax:+4952110689041.E-mailaddress:tauch@cebitec.uni-bielefeld.de(A.Tauch).0168-1656/$–seefrontmatter© 2009 Elsevier B.V. All rights reserved.doi:10.1016/j.jbiotec.2009.12.004

oftheregulatorynetwork.Thesepatternsofconnectionsincludesingleinputmotifs,bi-fanmotifs,feed-forwardloops,anddenseoverlappingregulons(Dobrinetal.,2004;Shen-Orretal.,2002).Beyondthat,autoregulation,multi-componentloopsandregula-torycascadeswerealsodescribedasnetworkmotifs(Yuetal.,2003).Inthecellularsystem,networkmotifsgenerallyarenotisolatedbutinterconnectedtocomplexstructures,formingthearchitecturalbackboneoftheTRN(Dobrinetal.,2004;MadanBabuetal.,2004).

NovelmethodsofultrafastDNAsequencingandgenome-widetranscriptionalpro lingwithtechniqueslikeDNAmicroarrayhybridizations,aswellascomputationalapproachesgeneratehugeamountsofdataontranscriptionalregulatoryprocessesinabacterialcell(Babu,2008;Ballezaetal.,2009).Overtheyears,considerableinformationhasbeenaccumulatedontranscriptionalregulationintheGram-negativemodelorganismEscherichiacoliandstoredinthereferencedatabaseRegulonDB(Collado-Videsetal.,2009).Currently,theTRNofE.coliisthemostdetailedreconstructionofregulatoryinteractionsinbacteria,providingvaluableinsightsintoitsglobaltopologicalorganization(Balajietal.,2007;Gama-Castroetal.,2008).Thiscomprehensivenetworkreconstructionrevealedamodularandhierarchicalstructureofregulatoryinteractionsatthetranscriptionallevel(Maetal.,2004;Resendis-Antonioetal.,2005).Recentresultsindicatedthatdiffer-entorganizationallevelsoftheTRNofE.coliarebridgedbythe