链霉菌I06A-00625与S12A次级代谢产物的分离纯化、结构鉴定

发布时间：2018-02-12 11:59

本文关键词： 铜绿假单胞菌抗真菌物质提取分离结构鉴定　出处：《北京协和医学院》2012年硕士论文　论文类型：学位论文

【摘要】：铜绿假单胞菌是一种条件致病菌,临床上常常感染免疫力低下的病人,引起菌血症、肺炎、泌尿系统感染等。由于抗生素的大量应用,导致铜绿假单胞菌突变的耐药菌存在着外排多种物质的主动外排系统,再加上铜绿假单胞菌的外膜通透性低,使其对多种抗生素的敏感度下降,使铜绿假单胞感染成为难以对付的医院内感染,因此迫切需要发现新的抗铜绿假单胞菌的药物。分泌途径(Sec途径)是细菌蛋白质转运的重要途径,通过它的转运,细胞内表达的蛋白质才能在细胞外发挥功能。SecAATP酶是Sec途径中唯一已知的能量转化酶,因此也是细菌生命过程中的关键酶,所以SecAATP酶可以作为抑制细菌的一个理想靶点。链霉菌I06A-00625是本所菌种中心通过建立铜绿假单胞菌SecA ATP酶抑制剂筛选模型得到的阳性菌株。菌种I06A-00625的发酵产物对铜绿假单胞菌及真菌均有抑制作用,我们利用大孔吸附树脂、葡聚糖凝胶、高效液相色谱等多种色谱手段对具有抗菌活性的组分进行分离纯化,得到了一个已知化合物丰加霉素(toyocamycin),以及三个具有抗真菌作用的已知四烯大环内酯类抗生素。另外还对抗水稻稻瘟菌阳性菌株S12A的代谢产物进行提取分离,得到了一个具有抗真菌作用的已知化合物放线菌酮(Cycloheximide)。
[Abstract]:Pseudomonas aeruginosa is a kind of conditional pathogen, which often infects patients with low immunity in clinic, causing bacteremia, pneumonia, infection of urinary system and so on. The drug-resistant bacteria that cause the mutation of Pseudomonas aeruginosa have active efflux system of many kinds of substances, in addition, the outer membrane permeability of Pseudomonas aeruginosa is low, and the sensitivity of Pseudomonas aeruginosa to a variety of antibiotics is decreased. Pseudomonas aeruginosa infection is an intractable nosocomial infection, so it is urgent to find new drugs against Pseudomonas aeruginosa. Secretory pathway (SEC pathway) is an important pathway for bacterial protein transportation.SecAATPase is the only known energy invertase in the Sec pathway. Therefore, it is also a key enzyme in bacterial life, so SecAATP enzyme can be used as an ideal target for bacterial inhibition. Streptomyces I06A-00625 is a positive strain obtained by establishing a screening model of Pseudomonas aeruginosa SecA ATP enzyme inhibitor. The fermentation products of strain I06A-00625 can inhibit both Pseudomonas aeruginosa and fungi. Dextran gel and high performance liquid chromatography (HPLC) were used to isolate and purify the antimicrobial constituents. A known compound, Fenggamycini, and three known macrolides with antifungal activity were obtained. In addition, the metabolites of the positive strain S12A against rice blast were extracted and separated, and a known antifungal compound, actinomycin Cycloheximidean, was obtained.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R378

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