Studies on terpenoids produced by actinomycetes-Screening for new bioactive compounds

放线菌产生的萜类化合物的研究——新型生物活性化合物的筛选

基本信息

批准号：
14360067
负责人：
SETO Haruo
金额：
$ 4.22万
依托单位：
Tokyo University of Agriculture
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14360067/
关键词：
terpenoid actinomycetes pimaradiene mevalonate pathway mevashuntin HMG-CoA reductase mevalonate pathway gene diterpene テルペン pimaradiene mevinolin フラキノシン Sterptomyces sp.CL190 naphterpin phenazinomycin furaquinocin MEP経路ト

项目摘要

The purpose of this project is to isolate new terpenoids from Actinomycetes and to investigate their chemical and biological properties. In order to achieve this purpose, we first attempted to isolate actinomycetes possessing the mevalonate pathway by using the HMG-CoA reductase gene as a probe for PCR, the key enzyme of the mevalonate pathway, and then to isolate terpenoids from the microorganisms. Contrary to our expectation, the number of positive strains isolated was very small, but we succeeded in purification of several new terpenoids. Among them, one compound proved to be a new diterpene derivative with the isopimaradiene skeleton that has never been isolated as actinomycetes metabolites. Although detail properties of this new compound can not be disclosed due to patent application, it showed strong inhibitory activity to EGF protein tyrosine kinase and its detailed biological activities are now under investigation. Another new terpenoid was also isolated from another strain of Streptomyces.In order to disclose the relationship between the mevalonate pathway and terpenoid biosynthesis, the relevant genes of actinomycetes producing terpenoids were investigated in this project. As a result, it turned out that genes related to terpenoid biosynthesis existed around the mevalonate pathway gene cluster. This finding shows that the mevalonate pathway is strictly linked to production of terpenoids. Expression of these gene was observed at the later stage of the growth of the producing organisms when the production of secondary metabolites started.Inhibition of the mevalonate pathway in one Streptomyces strain with the mevalonate pathway caused accumulation of a new compound, mevashuntin. The obtained information is expected to be important for studies related to production of terpenoids by actinomycetes.

该项目的目的是将新的萜类化合物与放线菌分离，并研究其化学和生物学特性。为了实现此目的，我们首先试图通过使用HMG-COA还原酶基因作为PCR，甲龙酸酯途径的关键酶，然后将甲戊烷的酶隔离，然后从微生物中分离terpenoids，然后将具有甲丙酸酯途径的放线菌分离。与我们的期望相反，分离的阳性应变数量很少，但是我们成功地纯化了几种新的萜类化合物。其中，一种化合物被证明是一种新的二萜衍生物，其异丙烯骨架从未被分离为放线菌的代谢产物。尽管该新化合物的细节特性无法由于专利的应用而披露，但它显示出对EGF蛋白酪氨酸激酶的强烈抑制活性，现在正在研究其详细的生物学活性。还从另一种链霉菌菌株中分离出了另一种新的萜类化合物。为了披露甲戊酸途径与萜类化合物生物合成之间的关系，在该项目中研究了产生萜类化合物的放线菌的相关基因。结果，事实证明，与萜类化合物生物合成有关的基因存在于甲谷酸酯途径基因簇周围。这一发现表明，甲戊酸途径与萜类化合物的产生严格相关。当次生代谢产物的产生开始时，在生产生物生长的后期观察到了这些基因的表达。抑制一种与甲龙酸酯途径的一种链霉菌菌株中的肠龙甲酸途径导致新化合物的积累。预期获得的信息对于与放线菌的萜类化合物有关的研究很重要。