【作者】 王浩宇；

【导师】 秦建春；

【作者基本信息】 吉林大学 ， 植物保护与资源利用（专业学位）， 2020， 硕士

【摘要】 多拉菌素（Doramectin）是一类新型大环内酯类抗寄生虫兽药,可安全高效驱杀牛、猪、羊等家畜体内和体表的寄生虫。目前,多拉菌素已经被研发和应用于市场二十余年,现在普遍应用于畜牧业生产。1975年,用于生产多拉菌素的阿维链霉菌（Streptomyces avermitilis）原始菌株被日本北里研究所从日本静冈县伊东市河奈的土壤中分离出来的。并在1976年由美国Merck公司将其鉴定,确定为链霉菌属里的一个新品种。阿维链霉菌在经过基因改造和生物合成后产生多拉菌素,这类菌素在动物体内的清除率更低、生物半衰期更长、生物利用率更高。因此多拉菌素成为目前生产的主要经济产物。在工业化生产中利用基因改造后的阿维链霉菌株可以提升多拉菌素的产量,但生产时附带合成的类似物杂质也给纯化带来难度,现代工厂粗放的分离提取工艺会使得多拉菌素的提取率不高。因此,对多拉菌素工业化生产排放的菌渣中残余的有效成分高效提取和开发利用十分必要。基于此,本实验采用工业化阿维链霉菌生产后的菌渣为研究对象,溶剂提取并测试杀虫活性,同时对多拉菌素纯度分析中相关的类似物杂质分离鉴定。该研究不但有望解决工业菌渣处理成本高的问题,同时变废为宝,为进一步开发生物农药打下基础。论文研究成果如下:1.以韭菜迟眼蕈蚊为研究对象,对多拉菌素的阿维链霉菌菌渣（简称多拉菌渣）提取物的乙酸乙酯萃取部分、石油醚萃取部分和正丁醇萃取部分进行了杀虫活性实验,比较各部分活性,确定多拉菌渣乙酸乙酯萃取部分杀虫活性较强。2.在多拉菌渣乙酸乙酯萃取部分分离得到5个与多拉菌素结构近似化合物。选择相对含量较多的YSYZ-DR2C（DR-IM3）进行结构鉴定,最终确定分子式为C₄₉H₇₂O₁₄,和多拉菌素的差别只是在14位碳上缺少一个甲基。通过对比文献,查阅相关数据,确定YSYZ-DR2C为新化合物。更多还原

【Abstract】 Doramectin is a new kind of macrolide antiparasitic veterinary medicine,which can drive away the parasites in cattle,pigs,sheep and other domestic animals safely and efficiently.At present,doramectin has been developed and applied in the market for more than 20 years,and now it is widely used in animal husbandry production.In1975,the original strain of Streptomyces avermitilis,which was used to produce doramectin,was isolated from the soil of Hanoi,ITO City,Shizuoka County,Japan,by the Kitasato University of Japan.It was identified as a new species of Streptomyces by Merck in 1976.After gene transformation and biosynthesis,Streptomyces avermitilis produces doramectin,which has lower clearance rate,longer half-life and higher bioavailability in animals.Therefore,doramectin has become the main economic product.In the industrial production process,although genetically modified Streptomyces avermitilis can increase the production of doramectin,the newly introduced impurities and extensive factory separation and extraction process will not maximize the economic value of doramectin.Therefore,it is very important to extract and isolate the industrial genetically modified residue of Streptomyces avermitilis and verify its biological activity.Based on this,industrialized Streptomyces avermitilis was used as the research object in this experiment to explore the unknown activity of its residue in depth.On the one hand,waste reuse can be achieved to increase the economic value of production,on the other hand,unknown components and their activities in impurities can be explored,which lays a foundation for the future development of biological pesticides.The research results are as follows:1.Taking Bradysia odoriphaga Yang et Zhang as the research object,the insecticidal activity experiments were carried out on the ethyl acetate part,petroleum ether part and n-butanol part of Streptomyces avermitilis residue（abbreviated as Dora residue）which produced doramectin.The activity of each part of Dora residue was compared,and it was determined that the ethyl acetate part of Dora residue had the best insecticidal activity.2.Five compounds with similar structure to doramectin were isolated from the ethyl acetate extraction part of Dora residue.YSYZ-DR2C（DR-IM3）with relatively high content was selected for structural identification,and the molecular formula was finally determined to be C₄₉H₇₂O₁₄.The difference between YSYZ-DR2C and doramectin was only the lack of a methyl group on the 14-Position carbon.YSYZ-DR2C was identified as a new compound by comparing the literature and consulting relevant data.更多还原