Study on biosynthetic machinery of type II polyketide synthase
| Project/Area Number |
18H02144
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 38040:Bioorganic chemistry-related
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Katsuyama Yohei 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (50646437)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
|
|---|
| Keywords | ポリケタイド / 生合成 / 放線菌 / 二次代謝 / 酵素 / polyketide / biosynthesis / enzyme / actinobacteria / secondary metabolite / enzymes / ポリエン / ポリケタイド合成酵素 / 芳香族化合物 / polyketide synthase / Streptomyces / natural products |
|---|
| Outline of Final Research Achievements |
We focused on the polyketides produced by actinomycetes and analyzed their biosynthesis. Twenty gene disruption strains were generated based on the yorpyrazone producer strain, and their metabolism was analyzed. The results showed that the biosynthetic intermediate of yoropyrazone is a griseusin derivative. Furthermore, we succeeded in reconstituting part of the biosynthesis of griseusin derivatives in vitro. We also analyzed a part of the biosynthetic pathway of fogacin in vitro. We also worked on the X-ray crystallographic analysis of a particularly interesting enzyme among them. We also analyzed how polyketide synthase regulates protein-protein interactions and efficiently produces secondary metabolites, and elucidated some of the mechanisms.
|
| Academic Significance and Societal Importance of the Research Achievements |
放線菌の生産する芳香族ポリケタイドは抗がん剤であるドキソルビシンのように有用な生物活性を持つものが数多く存在する。これらの生合成機構を深く理解することで、これらの化合物の生合成経路の人為的な改変を実現し、より生物活性の良い化合物や安定性の高い化合物の創出につながる。今回、生合成機構が未知であった芳香族ポリケタイドの生合成機構が複数明らかになった。また、これらの化合物の生合成にはタンパク質タンパク質間の相互作用メカニズムを理解することが大事であるが、それに関してもいくつかの重要な知見が得られた。本研究を継続し、これらの理解がさらに進めば新たな医薬品化合物候補の創出につながると期待される。
|
Report
(5 results)
Research Products
(13 results)
