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1、天津大學(xué)碩士學(xué)位論文達(dá)托霉素高產(chǎn)菌株選育及發(fā)酵條件優(yōu)化姓名:范晶華申請(qǐng)學(xué)位級(jí)別:碩士專業(yè):生物化工指導(dǎo)教師:聞建平20070101ABSTRACTDaptomycinisanewlipopeptideantibioticwhichcontainsaringwithteenaminoacidsandthreeaminoacidswitha10.carbondecanoicacidattachedtothetcrminalL-tryptophan.DaptomycinisproducedbyStreptomycesroseos
2、porus,anditsactivitylimitedtogram-positiveorganisms,especiallytheantibiotic-resistantbacteriasuchasStaphvlococcusaureus(MRSA),vancomycin-resistantenterococciWry).DaptomycinwasapprovedbyFDAin2003,anditwasusedinskinandsofttissueinfection.However,theinternalresearcho
3、fdaptomycinproductionisrare,sotheapplicationofdaptomycinislimitedseverely。Therefore,itisofgreatimportancetoenhancetheresearchanddevelopmentofdaptomycinproductionprocess.Inthiswork,thehighproductivitystrainWasselectedfordaptomycinproductionandthemediumcompositionan
4、dfermentationconditionswercoptimized.Themajorresearchcontentsandresultsareasfollows:,StreptomycesroseosporusLD-1wasused黼anoriginalstrain。Aftertreatedwithdiethylsulfateand1aserirradiationinseries,amutantstrainLD.54Wasscreenedoutbyusingthemediumwithselectivepressure
5、ofstreptomycin.Underthefermentationconditionwithoutbeingoptimized,theproductionofdaptomycinwas34.29m醣,whichwas1.94timeshi曲el"thanthatoftheparentalstrainLD一1二Thestrain始geneticallystable.Thebatchfermentationofdaptomycinproduction、)I,iththestrainLC一54inshakeflaskWaSs
6、tudied。TheoptimalseedageandthefermentationmediumfordaptomycinproductionweredesignedbyusingSAS.Also,theeffectsofcultivationconditionssuchasinoculum,rotatespeed,initialpHvalue,andculturemediumondaptomycinproductionbyStreptomycesroseosporu$wereevaluated.Undertheoptim
7、umconditions,strainLC一54couldproducedaptomycin54.5mg/ebyshaking—flaskbatchfermentation。whichwas58.9%higherthanthatofinitialconditions。TheeffectofprecursorondaptomycinproductionWasstudied.A7.5LbioreactorWasusedtostudythedaptomycinfermentation,theproductionofdaptomy
8、cinreached126.6mga.。intheoptimizedoperatingcondition,whichWas133%higherthanthatinshaking-flaskfermentation。AlogisticmodelWasadoptedtosimulatetheexperime