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Regulatory molecule cAMP changes cell fitness of the engineered

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MetabolicEngineeringxxx(xxxx)xxxPleasecitethisarticleas:Seong-HeeJeong,MetabolicEngineering,https://doi.org/10.1016/j.ymben.2020.11.009Availableonline24November20201096-7176/©2020InternationalMetabolicEngineeringSociety.PublishedbyElsevierInc.Allrightsreserved.RegulatorymoleculecAMPchangescellfitnessoftheengineeredEscherichiacoliforterpenoidsproductionSeong-HeeJeongb,1,Ji-BinParkb,1,YanWanga,Gye-HwanKimb,GaochuanZhanga,GongyuanWeia,ChonglongWanga,*,Seon-WonKimb,**aSchoolofBiologyandBasicMedicalSciences,SoochowUniversity,Suzhou,People’sRepublicofChinabDivisionofAppliedLifeScience(BK21Four),PMBBRC,GyeongsangNationalUniversity,Jinju,RepublicofKoreaARTICLEINFOKeywords:CellfitnesscAMPTerpenoidsAdenylatecyclaseMetabolicengineeringABSTRACTSTerpenoidsareaclassofnaturalcompoundswithmanyimportantfunctionsandapplications.Theyaresyn-thesizedfromalongsyntheticpathwayofisoprenylunitcouplingwiththemyriadsofterpenesynthases.Owingtothecatalyticdivergenceofterpenoidssynthesis,microbialproductionofterpenoidsiscompromisedtothecomplexityofpathwayengineeringandsuffersfromthemetabolicengineeringburden.Inthiswork,theadaptiveEscherichiacoliHPvariantexhibitedageneralcellfitnessinterpenoidsynthesis.Especially,itcouldyieldtax-adieneof193.2mg/Linatesttubeculture,whichisafive-foldincreaseovertheproductioninthewildtypeE.coliDH5α.MutationalanalysesindicatedthatIS10insertioninadenylatecyclaseCyaA(CyaAHP)resultedinloweringintracellularcyclicAMP(cAMP),whichcouldregulateitsreceptorproteinCRPtorewirecellmeta-bo

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