腸内微生物群に関連した結腸癌の分子基礎:合成的視点
Alan R Healy1,2, Seth B Herzon1,3
1Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
Journal of the American Chemical Society
|September 27, 2017
まとめ
研究者らは大腸がんに関連した コリバクチンのような 細菌代謝物を調べました 合成と生物合成の研究は,コリバクチンが遺伝子毒性イミンであることを明らかにし,DNAを損傷するメカニズムを確認した.
科学分野:
- 微生物学
- 自然製品化学
- 人間 の 健康
背景:
- バクテリアの代謝産物と人間の健康との因果関係を確立することは困難です.
- コメンスアル・エシェリキア・コライは,clb遺伝子クラスタを通じて,プレコリバクチンとコリバクチンを産生する.
- コリバクチンは,大腸がんに関与している疑われる遺伝子毒素です.
研究 の 目的:
- CLB メタボリートの構造と作用メカニズムの解明
- これらの化合物を理解する近年の合成と生物合成の進歩を活用する.
- 有効なコリバクチンの遺伝子毒性と化学クラスを確認する.
主な方法:
- CLB遺伝子群とその産物を研究するために遺伝的アプローチを活用した.
- 合成化学の取り組みは 生物合成の洞察に基づいています
- コリバクチンペプチダゼClbPを削除した影響を調査した.
主要な成果:
- ClbPの除去により,遺伝子毒性のないピリドン基化合物が生じる.
- 活性遺伝子毒素 (コリバクチン) は不飽和イミンとして識別される.
- これらのイミンは前述の仮説を裏付ける 強力なDNA破壊物質です
- バクテリア抽出物におけるイミンの検出は最近であり,分離は困難である.
結論:
- 最近の合成および生物合成研究により,CLBの代謝産物の作用メカニズムが明らかにされました.
- コリバクチンは,遺伝子毒性の不飽和イミンで,DNAの損傷を起こすことが確認されています.
- 合成と生合成の研究の相互作用は,将来の天然製品の発見にとって極めて重要です.
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