2021 Fiscal Year Final Research Report
Chemical communications in microbial interactions and development of useful bioactive ligands
| Project Area | Frontier research of chemical communications |
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| Project/Area Number |
17H06401
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井本 正哉 順天堂大学, 大学院医学研究科, 特任教授 (60213253)
西村 慎一 東京大学, 大学院農学生命科学研究科(農学部), 講師 (30415260)
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| Project Period (FY) |
2017-06-30 – 2022-03-31
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| Keywords | 化学コミュニケーション / 天然物化学 / 複合培養 / 生物活性リガンド / 生合成 |
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| Outline of Final Research Achievements |
Biosynthetic pathway of antifungals 5aTHQs and antibiotics STAMs, which are produced by combined-culture of Streptomyces sp. HEK616 and Tsukamurella pulmonis TP-B0596, were revealed. Moreover, antifungals 5aTHQs were shown to form aggregates that show enhanced membrane affinity and biological activity. Additionally, inspired by an extremely rare natural products yaku’amids, novel highly sensitive labeling reagents that would be powerful tools for scarce chemical communication molecules (natural products) were designed and synthesized, enabling us the development of highly sensitive advanced Merfey’s method. Furthermore, an innovative anticancer prodrug CMG (curcumin monoglucuronide) was developed, demonstrating not only its potent antitumor activity in oxaliplatin-resistant colon cancer but also its multiple sclerosis modulator with altered gut microbiota.
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| Free Research Field |
生物分子化学、ケミカルバイオロジー
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| Academic Significance and Societal Importance of the Research Achievements |
Tsukamurella pulmonis TP-B0596株を活用した複合培養系の汎用性が示されつつあることに加えて、5aTHQs及びSTAMsがいずれも新規なII型PKSによって生合成されることを明らかにしたことは、学術的にも意義深い。また、極微量の化学コミュニケーション分子や各種アミノ酸などの高感度ラベル化剤の開発は、今後の希少天然物などの探索・同定に大きく寄与する。本研究課題で得られた多くの研究成果は、生物活性リガンドを起点とした化学コミュニケーションの理解と制御に学術的に貢献するとともに、医薬品や農薬などの開発に寄与することが期待される。
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