| Project/Area Number |
14360067
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | Tokyo University of Agriculture |
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Principal Investigator |
SETO Haruo Tokyo University of Agriculture, Biological Applied Chemistry, Professor, 応用生物科学部・生物応用化学科, 教授 (10013335)
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| Co-Investigator(Kenkyū-buntansha) |
SUE Masayuki Tokyo University of Agriculture, Biological Applied Chemistry, Assistant Professor, 応用生物科学部・生物応用化学科, 助手 (10328544)
FURIHATA Kazuo University of Tokyo, Graduate School of Agricultural and Life Sciences, 大学院・農学系研究科, 助手 (20219091)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | 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 / トリテルペン化合物 / helvolic acid |
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| Research Abstract |
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.
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