喜树碱的生物合成途径及生物技术研究进展

,,X(,400715):,,:;;;;:R28211:A:02532670(2006)04062304AdvancesinstudiesonbiosyntheticpathwayandbiotechnologyofcamptothecinLILian2qiang,PANXi2chun,TANFeng(KeyLaboratoryofEco2environmentsinThreeGorgesReservoirRegion,MinistryofEducation,SchoolofLifeScience,SouthwestChinaUniversity,Chongqing400715,China)Keywords:camptothecin;biosyntheticpathway;syntheticorgan;callus;hairyroot(camptothecin)1966WallCamptothecaacuminataDecaisneErvatamiaheyneana(Wall1)T1Cooke,Nothapodytesfoetida(Wight)Sleumer,OphiorrhizapumilaChamp1exBenth1[1]DNAÉ(DNAtopoisomeraseÉ),2090[2]FDA,(Irenotecan)(Topotecan),,[3]2010,10[4],600kg,;,,,,,1,1.52.5,,[5]Yamazaki[6],,(),(strictosidinesynthase,SSS),,,,;[7]1994,Lopez2Meyer:,;,[8],,,,Lopez2Meyer[9],,[10],[6],,2211:,326ChineseTraditionalandHerbalDrugs37420064X:2005208208:(1981),,,Tel:[phone]Fax:[phone]E2mail:[e-mail]3Tel:[phone]E2mail:[e-mail]:023(68252365)©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.:B;TDC:;DXS:252;DXR:252;MECS:22C22D222,42;G10H:2102;SCS:;SSS:;102HGO:102Multiplearrowsindicatemultiplestepsbetweenintermediates;TSB:B2subunitoftryptoophansynthase;TDC:tryptoophandecarboxylase,DXS:12deoxy2D2xylulose252phosphatesynthase;DXR:12deoxy2D2xylulose252phosphatereductoisomerase;MECS:22C2methyl2D2ery2thritol22,42cyclodiphosphate2synthase;G10H:geraniol2102hydroxylase;SCS:secologaninsynthase;SSS:strictosidinesynthase;102HGO:102hydroxygeranioloxidoreductase.1Fig.1Biosyntheticpathwayofcamptothecin(mevalonatepathway,MVA),[11],(methylerythritolphosphate,MEP)(isopentenyldiphos2phate,IPP)Yamazaki[12][1213C],[fos2midomycin62A2(lovastatin)],(lo2ganin)MEP,,[13],(tryptophan)[14]Ya2mazaki[12]:(TDC)(tryptamine),,(strictosidine),1200(strictosamide),3(S)2pumiloside3(S)2deoxypumiloside426ChineseTraditionalandHerbalDrugs37420064©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.[15]212:,Whitmer[16]:102,1022102(G10H),,G10HCollu[17]G10H,cDNA,CYP76B6G10H,G10H,G10HCanto[18]G10H,G10H,G10H,G10HG10H,,Andrea[19]CG1,,:,,:11dCG10.1pkat,1.1pkat,10400pkat,CG1,,213:,tdc1tdc2hmg1hmg2hmg3tsb10hgo(1)1Table1ClonedgeneassociatedwithcamptothecinbiosyntheticpathwayTsb[20]BTSBtdc1[21]tdc2[21]TDC,MeJahmg1[22]hmg2[23]hmg3[23]32232CoAHMGRHCPT,MeJaMeJaMeJasss[11]strNAA10hgo[24],,3311:,,SakatoMis2avaVanHengelWiedenfied[9],[25],,,0.02%,33.3%50%Helmut[26]102312:[27],,AgrobacteriumrhizogenesRiT2DNA,,,,,,,,Devanand[28],MS,,:MSNAA(71.36LmolöL)BA(8.87LmolöL)(0.01%)92(0.0016%)Saito[29],1mg,DiaionHP220(,),,,Sudo[30]526ChineseTraditionalandHerbalDrugs37420064©1994-2007ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(3.6mg);(5),3LLorence[31]ATCC15834R21000,ATCC15834,102(1.0mg0.15mg),421,,,,,,,,,,,,,,,References:[1]LorenceA,NesslerCL1Camptothecin,overfourdecadesofsurprisingfindings[J]1Phytochemistry,2004,65:2735227491[2]HanR1AnticancerDrugResearchandExperimentalTechno2logy()[M]1Beijing:BeijingMedicalUniversityandChineseUnionMedicalUniversityUnitePress,19971[3]ZhangXQ,TangJG,YiY,etal1CamptothecaacuminateresourcesandpersistenceexploitationcountermeasureofChina[J]1JGuizhouNormUniv:NatSci(:),2004,2:362391[4]LiB,MaJ,FuL1Synthesisof102hydroxycamptothecin1[J]1JBeijingUnivChemTechnol(),2004,31(1):712741[5]ChenY,CaoFL,LiSX,etal1AdventitiousbudinductionandplantletregenerationofCamptothecaacuminate[J]1PlantPhysiolCommun(),2004,40:57925831[6]YamazakiY,UranoA,SudoH,etal1Metaboliteprofilingofalkaloidsandstrictosidinesynthaseactivityincamptothecinproducingplants[J]1Phytochemistry,2003,62:46124701[7]ZuYG,TangZH,YuJH,etal1Camptothecinand102hy2droxycamptothecinaccumulatedifferentiallyunderspecificdevelopmentalcontrolinCamptothecaacuminata[J]1ActaBotSin,2003,45(4):49424991[8]Lopez2MeyerM,NesslerCL,McKnightTD1Sitesofac2cumulationoftheantitumoralkaloidcamptothecininCamp2tothecaacuminata[J]1PlantaMed,1994,60:55825601[9]ZhangDY,ZhaoXQ,YuF,etal1CallusinductionofCamptothecaacumiantaandcamptothecinproduction[J]1JNortheastNormUniv:NatSci(:),2002,34,(1):452481[10]LiuWZ1Secretorystructuresandtheirrelationshiptoaccu2mulationofcamptothecininCamptothecaacuminata(Nys2saceae)[J]1ActaBotSin,2004,46(10):1242212481[11]RohmerM1Amevalonate2independentroutetoisopentenyldiphosphate[J]1ComprehNatProdChem,1999,2:452671[12]YamazakiY,KitajimaM,AritaM,etal1Biosynthesisofcamptothecininsilicoandinvivotracerstudyfrom[12[13]C]2glucose1[J]1PlantPhysiol,2004,134:16121701[13]EisenreichW,RohdichF,BacherA,etal1Adeoxyxylulosephosphatepathwaytoterpenoids[J]1TrendsPlantSci,2001,6:782841[14]SherihaGM,RapoportH1BiosynthesisofCamptothecaacuminataalkaloids[J]1Phytochemistry,1976,15:50525081[15]KitajimaM,YoshidaS,YamagataK,etal1Camptothecin2relatedalkaloidsfromhairyrootsofOphiorrhizapumila[J]1Tetrahedron,2002,58:9169291781[16]WhitmerS,CanelC,HallardD,etal1InfluenceofprecursoravailabilityonalkaloidaccumulationbytransgeniccelllineofCantharanthusroseus[J]1PlantPhysiol,1998,116:85328571[17]ColluG,UnverN,Peltenburg2LoomanA,etal1Geran