| Project/Area Number |
17K19243
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Agricultural chemistry and related fields
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| Research Institution | Fukui Prefectural University |
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Principal Investigator |
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| Research Collaborator |
MARUYAMA Chitose
NIIKURA Haruka
MATSUDA Kanki
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | tRNA / ペプチド合成酵素 / ペプチド / 生合成 |
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| Outline of Final Research Achievements |
Transfer RNA (tRNA)-dependent amide bond forming enzymes are reported to be involved in the biosynthesis of peptide natural products from Streptomycetes by hijacking aminoacyl-tRNAs from protein biosynthesis. Recently, we also identified two tRNA-dependent enzymes, Orf11 and Sba18, which are involved in the biosynthesis of glycylthricin; they catalyze a condensation reaction between the biosynthetic intermediates, Gly-tRNA and aminosugar, via amide bond. Although Orf11 can accept only the Gly-tRNA as a substrate for the amide bond formation, Sba18 shows a promiscuous substrate specificity against aminoacyl-tRNAs, producing not only glycylthricin but also two novel grycylthricin-related compounds. Therefore, a better understanding of the substrate specificity of Sba18 would generate novel unnatural natural compounds by chemoenzymatic synthesis. Indeed, the unique substrate specificity of Sba18 gave us 14 new compounds related to glycylthricin.
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| Academic Significance and Societal Importance of the Research Achievements |
抗がん剤、抗生物質、抗ウイルス剤など現代に無くてはならない医薬品については、より多くの新薬開発が世界的に求められている。その新たな戦略として、様々な理由から未利用のままである天然由来生理活性物質について、生合成研究から見出した生合成酵素を活用し、化学構造の多様性を創出することが可能になれば、新たな医薬品リード化合物の創製につながると考えられる。抗生物質streptothricin(ST)も未利用資源の一つであり、我々が見出した新規アミド合成酵素の活用は、STの臨床利用への可能性が期待できる。
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