2023 Fiscal Year Final Research Report
Bioorganic studies on the genotoxicity of colibactin produced from human microbiome in colorectal cancer
| Project/Area Number |
20K05849
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38040:Bioorganic chemistry-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 腸内細菌 / バイオーム分子 / 天然物化学 / コリバクチン / ヒューミマイシン / 標的探索 / プロバイオティクス / 片利共生 |
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| Outline of Final Research Achievements |
There is a large number of ectoparasitic microbiota in human intestine, where a commensalistic relationship is established. These imbalances can lead to cancer and neurodegenerative diseases, but the structure and mode of action of secondary metabolites ("biome molecules") related to the pathology are still largely unknown. In this study, we investigated colibactin produced by Escherichia coli and humimycin produced by Rhodococcus spp. using organic synthesis, structure-activity relationship study, and target ID method. The results suggest that cyclopropane rings and planar structures may be required for DNA binding in the genotoxicity of colibactin. Humimycin analogues showed potent DNA binding activity as well as antibacterial activity against pathogens related to the food industry.
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| Free Research Field |
ケミカルバイオロジー
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| Academic Significance and Societal Importance of the Research Achievements |
近年，ヒトの腸内における微生物群と疾患との関連性は各種オミクス解析によって明らかになりつつある．一方，疾患に関わりがある微生物が複数種同定されているものの，片利共生のインバランスのトリガーになりうる2次代謝物（バイオーム分子）の構造や作用機構などその実体は不明な点が多い．本研究では，代表的なバイオーム分子2種を例に挙げて，それらの遺伝毒性や抗菌活性に重要な役割を果たす構造因子の基礎的な知見を得たことは学術的に意義深い．特に，ヒューミマイシン類縁体が食品産業と関わりの深い病原菌に対して強い抗菌活性を示すことを明らかにしたことは，今後の社会的有用性を予見させるものである．
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