Studies on development of a new production method for anti-cancer agent, taxol by use of pestalotiopsis sp.

利用拟盘菌开发抗癌剂紫杉醇新方法的研究。

基本信息

批准号：
14560138
负责人：
TACHIBANA Sanro
金额：
$ 2.3万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Using a taxol producing fungus isolated from Kyaraboku (Taxus cuspidata var. nana), improvement of taxol productivity by change of incubation conditons and othe methods by mutation and cell fusion of the fungus were conducted. And, taxol productivity was examined by the newly isolated fungi from inner bark of genus taxus trees. The following results were obtained.(1)The trial for increase in the taxol productivity : Culture methods were changed from standing cultures to shaking and immobilized cultures. However, the taxol productivity was about 1/10 times to the standing cultures. Effect of sugar as a biogenetic precursor on taxol production was examined by change the sugar composition and added amount of sugar in the medium. It was found that taxol productivity was increased 1.3 times when glucose and small amount of myoinositol was added to the culture. And, taxol productivity was tried to increase by addition of a biogenetic inhibitor. But, the productivity could not be increased. F … More urthermore, the effect of taxol productivity on change of added amount of nitrogen in the culture medium was examined. It was found that taxol productivity was increased 1.3 times when the amount of nitrogen was decreased 1/10 times. It was found that a kind of taxane compound (elucidated the structure) was produced except for taxol by the culture of the fungus.(2)The fungus was made to mutate by ultraviolet irradiation and chemical reagent. But, taxol productivity was not increased when each mutation fungus was incubated in the culture medium. And, the formation of fusants having higher taxol productivity was tried by protoplast fusion of the fungus. The taxol productivity by cultures of the fusants is being conducted.(3)Increase in taxol productivity : It was found that taxol productivity was drastically improved, when taxol production by fermentation of the fungus is used jointly with taxol production by immobilized cell cultures of Kyaraboku in a bioreactor. And, taxol productivity of some newly isolated fungi from genus taxus trees was examined. It was found that one newly fungus had higher taxol productivity than the fungus used in the research. And furthermore, it was found that antifungal activity of taxol produced by the fungus present in inner bark of Taxus cuspidata van nana are related to the antifungal activity of wood extracts. Less

使用从kyaraboku（taxus cuspidatavar。Nana）分离出的紫杉醇，通过改变孵化条件的变化来改善紫杉醇生产，而其他方法通过真菌的突变和细胞融合进行了方法。而且，紫杉醇的生产是由新近隔离的真菌从属于出租车属的内部树皮中检查的。（1）提高紫杉醇生产力的试验：培养方法从持久文化变为摇动和固定的培养物。但是，紫杉醇生产率约为常规文化的1/10倍。通过更改糖成分和培养基中添加量的糖分，检查了糖作为生物遗传学先驱对紫杉醇产生的影响。发现当葡萄糖和少量肌醇添加到培养物中时，紫杉醇生产率提高了1.3倍。并且，试图通过添加生物遗传学抑制剂来提高紫杉醇生产率。但是，生产率无法提高。 f…更urthermore，研究了紫杉醇生产力对培养基中添加量的氮的变化的影响。发现当氮量减少1/10倍时，紫杉醇生产率提高了1.3倍。发现除了真菌的培养物外，还产生了一种紫杉烷化合物（阐明结构）。（2）真菌是通过紫外线辐照和化学试剂突变的。但是，当在培养基中孵育每种突变真菌时，紫杉醇生产力并没有提高。而且，通过真菌的原生体融合，尝试了具有较高紫杉醇生产率的融合的形成。（3）紫杉醇生产率的提高：发现紫杉醇生产率得到了巨大提高，当紫杉醇生产力得到了巨大提高，当紫杉醇通过发酵而产生的紫杉醇生产与生产真菌的发酵共同使用，由含符号的甲状腺酸含量通过固定的kyaraboku细胞培养物，kyaraboku的kyaraboku in Bioreactor中。而且，检查了一些新近孤立的真菌与属属属树木的生产力。发现一种新的真菌的生产率高于研究中的真菌。此外，发现存在于甲壳虫cuspidata van Nana内的真菌产生的紫杉醇的抗真菌活性与木材提取物的抗真菌活性有关。较少的