マダガスカル・ペリウィンクルの抗がん剤ヴィンブラスティンの生合成に欠けている酵素

Lorenzo Caputi¹, Jakob Franke¹, Scott C Farrow¹

¹Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.

Science (New York, N.Y.)

|May 5, 2018

まとめ

研究者らは,ヴィンブラスティンの生物合成のためのカタランス・ローゼスの鍵となる酵素を特定した. この発見は,植物化学の多様性を理解し,この抗癌薬の新たなソースを開発するのに役立ちます.

科学分野:

植物生化学
自然製品の生物合成
薬用植物化学

背景:

ヴィンブラスティンはカタランタス・ローゼス (Catharanthus roseus) から得られた重要な抗がん剤です
現在の生産量は限られており,代替調達戦略が必要である.
複雑な生物合成経路は完全な遺伝子識別を妨げています

研究の目的:

ヴィンブラスティンの生物合成経路に欠けている酵素を特定するために
ヴィンブラスティンの前駆体となる化学的変異を解明する.
ヴィンブラスティンおよび関連化合物の異質生産を可能にします.

主な方法:

酸化酵素と還元酵素の活性を特徴付ける酵素測定法
ステマデニンアセテートイソメリゼーションの生化学分析
先駆体形成に関与する水溶剤の識別と特徴付け.

主要な成果:

ステマデニンアセテートのイソメリゼーションを触媒する2つの重要な酵素である酸化酵素と還元酵素が特定されました.
カタランチンまたはタバーソニンの形成につながる2つの水溶剤が特徴付けられました.
ヴィンブラスティン経路の重要な部分における完全な酵素的ステップが解明されました.

結論:

特定された酵素は,ビンブラスティンの生物合成の重要な部門の理解を完了します.
この研究は,ビンブラスティンの生産のための工学的な植物や微生物システムの開発を容易にする.
この発見は,植物由来化学の多様性と薬剤発見の理解に寄与する.

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