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ID:27212543
大小:1.41 MB
页数:53页
时间:2018-12-01
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1、第九章:抗生素的生产王雪青2003.12.15抗生素的生产概述抗生素的分类抗生素的应用半合成抗生素青霉素的生产和提取工艺抗生素的生产定义:是生物在其生命过程中产生的,并在低浓度下有选择性地抑制或杀灭其它微生物或肿瘤细胞的有机物质。MicrobialProducts,effectiveatlowconcentrations,whichhavetheabilitytokillorinhibitthegrowthofcertainmicro-organisms.History:19世纪70年代,法国Pasteur,发现有些微生物可以抑
2、制炭疽杆菌,提出了利用微生物抑制另一种微生物的现象来治疗一些感染性疾病。1928年,概述In1928ScottishbacteriologistAlexanderFlemingreportedtheantibacterialactionofculturesofaPenicilliumspeciesHeobservedthatPenicilliumnotatumkilledsomeofhisStaph.aureusculturedishesDiscoverybyaccident?Culturedishescontaminatedw
3、henleftoutfortwoweekswhileFlemingwasonholiday,insteadofbeingincubatedFlemingnoticedthatthesubstancesecretedwasaninhibitorofmanybacterialspeciesHepublishedapaperontheactiveingredientwhichhecalled‘penicillin’.Thiswasthefirstdemonstrationthatasubstanceproducedbymicro-or
4、g’scouldinhibitorkillothermicrobesFlemingcouldnotisolatepenicillin.10yrslaterscientistsFloreyandChainsuccessfullyisolatedpenicillin.1943-1945,scale-upproductionofpencillium.By1945,enoughpenicillinwasproducedtotreat7millionperyear.DiscovererofpenicillinBornintoafarmin
5、gfamilyinScotland,movedtoLondonat13AwardedScholarshiptostudymedicineAlexanderFlemingZoneofInhibitionThispictureillustratestheeffectofpenicillinonafungus.Notetheclearringofinhibition.ItwasthisobservationwhichinitiatedFleming’sfurtherstudies.HowardFloreyAustralian-born
6、StudiedScience&MedicineinAdelaideAwardedScholarshipatOxfordUniversityReturnedtoEnglandtocompleteaPhDErnstChainOfRussian-GermandescentGraduatedinChemistryandPhysiologyLeftBerlinwhenNazi’scametopowerHiredbyFloreytoworkonpenicillinproject到目前为止,有8000多种抗生素,2/3是由放线菌(strepo
7、myces)产生的,并通过化学结构的改造,总共有3万多种半合成抗生素,它们的分子量为100-1200,普遍应用的包括半合成和盐类的抗生素有350多种,其中以青霉素、头孢霉素、四环素类、氨基糖苷类和大环内脂类主要抗生素的使用量(Harvey,1998)抗生素种类用量(kg/year)动物1996人类1997/1998头孢类四环类氨基糖类大环内酯类121,603323,15137,05871,222314,49847,5005,40947,696SomeClinicallyImportantAntibioticsAntibiotic
8、sProducerOrganismActivitySiteormodeofactionPenicillinPenicillinchrysogenumGram-positivebacteriaWallsynthesisBacitracinBacillussubti
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