Project/Area Number |
26560428
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Biomolecular chemistry
|
Research Institution | The University of Tokyo |
Principal Investigator |
Abe Ikuro 東京大学, 薬学研究科(研究院), 教授 (40305496)
|
Co-Investigator(Kenkyū-buntansha) |
AWAKAWA Takayoshi 東京大学, 大学院薬学系研究科, 助教 (80609834)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | ポリケタイド合成酵素 / 生合成 / 遺伝子 / 生合成工学 / 合成生物学 / ポリエン化合物 |
Outline of Final Research Achievements |
The aim of this study is to elucidate the evolutionary relationship of polyketide synthases through comparison of the amino acid sequences of several polyene synthases. The chemical structure of a new precursor of a polyene, tetrafibricin, was determined, and the compound was named neotetrafibricin. The amino acid sequence of neotetrafibricin synthase was compared with other polyene synthases through bioinformatic ways, resulting in the finding of a key motif which determines a starter substrate specificity. In addition, we elucidated the crystal structure of AntE, an enzyme which provides a polyketide synthase with an extender unit. Based on AntE’s structure, we enlarged the range of substrate specificity of AntE, leading to the production of new antimycin compounds. These results will pave the way for future studies to engineer module-type polyketide synthases.
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