2021 Fiscal Year Final Research Report
Chemical characterization of colibactin and understanding a mechanism of an onset of colorectal cancer by colibactin
| Project/Area Number |
19H02898
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 38040:Bioorganic chemistry-related
|
|---|
| Research Institution | University of Shizuoka |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | コリバクチン / 天然物 / 生合成 / 大腸がん |
|---|
| Outline of Final Research Achievements |
In this research, using the high-colibactin-producing wild-type E. coli strain isolated from a clinical sample, we were able to identify colibactin 770, along with a more stable derivative, colibactin 788, which was further stabilized by converting the diketone moiety into quinoxaline in situ in the crude culture extract to form colibactin 860. The structure of colibactin 860 determined by NMR revealed a hydrolysis and rearrangement reactions performed to transfer the cyclopropanes in colibactin 770 to cyclobutanes in colibactin 788. Furthermore, colibactin 420 and 430 derived from alcoholysis of colibactin were also isolated and determined. The stereochemistry analysis of colibactin 860, 420, and 430 further confirmed the proposed mechanism of the rearrangement reaction.
|
| Free Research Field |
天然物化学
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は物質科学としての理解が化学のみならず医学に対してもインパクトを与えるものとなったと考えられる.最近はMSデータのみの論文もよく見かけるが、NMRを駆使しての精密構造解析の「単離構造決定」が最先端科学であることを改めて示した研究成果と言える. それとは別に、構造解析の研究テーマ自体が,がん治療にまで影響を与えたことになり,これは医学へと直結する. 化学構造の解析データそのものは小さいことでもゲノム情報に対する知見に化学的なプラスアルファがあれば,合理的な理解から導き出される革新的な治療への道が拓かれると感じている.
|
