具有产生安莎类抗生素潜能的放线菌的分子筛选论文

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1、具有产生安莎类抗生素潜能的放线菌的分子筛选论文武临专张会图韩锋高群杰孙桂芝王以光【摘要】目的建立一种高通量筛选具有产生安莎类抗生素潜能的放线菌的分子筛选方法。原理3氨基5羟基苯甲酸(AHBA)是安莎类抗生素生物合成的前体。在通过氨基莽草酸途径生物合成AHBA的过程中，AHBA合酶是催化5氨基3脱氢5脱氧莽草酸形成AHBA的一个特异性关键酶。AHBA合酶基因的存在可以作为放线菌菌株具有合成安莎类抗生素能力的一个必要而非充分的条件。AHBA合酶基因高度保守.freelycinsarecharacterizedbyabenzenicornaphthalenicquino

2、idbasedchromophoreophoreidelinkage(Fig.1).ThechromophoreisgeneratedfromamC7Nunitderivedfrom3amino5hydroxybenzoicacid(AHBA)viaaminoshikimatepathainingpartofthechromophore,andtheansabridgearepolyketidederived.Fig.1AllansamycinsuseAHBAasthestarterunitfortheirbiosynthesisAnsamycinsshopicin,ase

3、misyntheticderivativeofrifamycinproducedbyAmycolatopsismediterranei,isoneofthemosteffectiveclinicaltreatmentsofmycobacterialinfection.17allylaminodemethoxygeldanamycin(17AAG),asemisyntheticderivativeofgeldanamycinproducedbyStrepromyceshygroscopicus,iscurrentlyunderclinicaltrialsfortumortrea

4、tment［1,2］.Ansamycinsarealsopotentialantiviralagents.Forexample,rifamycincouldblocktheRNAdependentDNApolymerasesofretroviruses,geldanamycincouldinhibitthereplicationofHerpesSimplexVirustype1(HSV1)invitro［3］.Screeningofnovelansamycins(andtheirproducers)isofgreatimportanceindiscoveringpromisi

5、ngdrugcandidatesorleadpoundsycinsproducedbystreptomycesstrainsycinsandcytotrieninA,bothofthemshooractivities［4～7］.Somenovelansamycinseansofchemicaland/orbiologicalmodificationsofknoycins［8］.Uptonoostnaturalansamycinsarediscoveredbyactivitybasedscreeningofmicrobial(especially,actinomycetes)fe

6、rmentationandextractionofproducts.Thatis,.freelodelycins,theirobviousdisadvantagesinclude:①thelimitationsofthefermentationconditionandtheminimalbioactivitydetectionleadtomissingthepotentialansamycinintheinitialscreening;②thestructuredeterminationplexityofnumerousrelatedchemistryresultedinblind

7、foldlaboriouseffortsforaimedscreeningofansamycin;③thedifficultiesinsettingupthehighthroughputscreeningprogram.aterialsandmethods1.1StrainsSevenstrainsproducingantibioticsotherthanansamycins,StreptomycesgriseolusCPHCC200279foranisomyci