SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors 英文参考文献.docVIP

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SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors 英文参考文献.doc

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SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors 英文参考文献

Horbaletal.AMBExpress2012,2:1 /content/2/1/1 ORIGINAL OpenAccess SimReg1isamasterswitchforbiosynthesisand exportofsimocyclinoneD8anditsprecursors LiliyaHorbal1,YuriyRebets1,MariyaRabyk1,RomanMakitrynskyy1,AndriyLuzhetskyy2,VictorFedorenko1and AndreasBechthold3* Abstract Analysisofthesimocyclinonebiosynthesis(sim)geneclusterofStreptomycesantibioticusTü6040ledtothe identificationofaputativepathwayspecificregulatorygenesimReg1.InsilicoanalysisplacestheSimReg1protein intheOmpR-PhoBsubfamilyofresponseregulators.GenereplacementofsimReg1fromtheS.antibioticus chromosomecompletelyabolishessimocyclinoneproductionindicatingthatSimReg1isakeyregulatorof simocyclinonebiosynthesis.ResultsoftheDNA-shiftassaysandreportergeneexpressionanalysisareconsistent withtheideathatSimReg1activatestranscriptionofsimocyclinonebiosynthesis,transportergenes,regulatory genesimReg3andhisowntranscription.Thepresenceofextracts(simocyclinone)fromS.antibioticusTü6040× pSSimR1-1coulddissociateSimReg1frompromoterregions.Apreliminarymodelforregulationofsimocyclinone biosynthesisandexportisdiscussed. Keywords:Simocyclinone,angucycline,regulation,transport Introduction the activity of the pathway-specific regulatory genes, Theactinomycetes,includinginparticularmembersofthe whicharebelievedtobefinalcheckpointsintheonsetof genusStreptomyces,aretheindustrialsourceforalarge antibioticproductionAriasetal.1999;Nuriaetal.2007; numberofbioactivecompoundsemployedasantibiotics vanWezeletal.2009;Pulsawatetal.2007;Wangetal. andotherdrugsHorinouchi2007;BibbandHesketh2009. 2009.Becausemostantibioticsarepotentiallylethaltothe Actinomycetesproducethesemoleculesaspartoftheir producing organism, theonsetofantibiotic production ‘’secondary’’ornonessentialmetabolismvanWezeletal. should beunder tight control andmechanisms ofself- 2009.ManyStreptomycesspeciesarecapableofproducing resistance of producing bacteria must exist. All this morethanonesecondarymetaboliteOhnishietal.2008; requires