| Project/Area Number |
25850050
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied microbiology
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 生合成 / マクロラクタム抗生物質 / β-アミノ酸 / ATP依存型リガーゼ / X線結晶構造解析 / ポリケチド / 微生物酵素 / 結晶構造解析 |
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| Outline of Final Research Achievements |
Macrolactam antibiotics such as vicenistatin and cremimycin contain various beta-amino acids at the starter position of the polyketide backbone. In their biosynthesis, a standalone ATP-dependent ligase serves as a gatekeeper for a specific beta-amino acid recognition and activation. However, the beta-amino acid recognition mechanism of ATP-dependent ligases remains elusive. To elucidate the beta-amino acid recognition mechanism, we carried out the structural and mutational studies of the ATP-dependent ligases including VinN, which activates 3-methylaspartate in vicenistatin biosynthesis and CmiS6, which activates 3-aminononanoate in cremimycin biosynthesis. The VinN structure complexed with 3-methylaspartate provides detail mechanistic insights into the selective recognition of beta-amino acids in this family of enzymes. We also identified the biosynthetic gene cluster of hitachimycin, which is another macrolactam compound.
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