モロイドンペプチドの遺伝子誘導発見とリボソーム生物合成

Roland D Kersten¹, Lisa S Mydy¹, Timothy R Fallon^2,3

¹Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.

Journal of the American Chemical Society

|April 19, 2022

まとめ

科学者は,モロイドンペプチドは,リボソーム合成と翻訳後の改変 (RiPP) 経路を使用して植物によって作られていることを発見しました. これは植物由来がん治療の開発に新たな道を開きます

科学分野:

生物化学
植物学
薬物の発見

背景:

植物性ペプチドであるモロイディンは癌治療薬としての可能性を示していますが生産するのは困難です
既存の分離と合成方法では薬の開発を制限する低量の産物が得られる.

研究の目的:

モロイドン型バイサイクルペプチドの代替生産経路として生物合成を調査する.
植物におけるモロイドンの生物合成に責任を負う酵素を特定する.

主な方法:

モロイドンの前駆体ペプチドとサイクラスを識別するための鉱山植物トランスクリプトーム.
日本のケリア・モロイドン・サイクラスの機能を特徴づけている.
遺伝子組み換えたばこ植物でセロゲンチンCを含む様々なモロジンを生成する.

主要な成果:

モロイドン型ペプチドは,BURP領域のペプチドサイクラスを介してリボソーム合成され,翻訳後の改変 (RiPPs) される.
日本のケリアから新しいモロイドン・サイクラスが特定され,特徴づけられました.
トランスジェニックたばこ植物は,肺腺がん細胞に対して細胞毒性を示すセルゲンチンCを成功裏に産生した.

結論:

生物合成はモロイドン型ペプチドの生産に適した代替手段である.
植物トランスクリプトームの採掘は,新しい生物活性サイクルペプチドとその酵素を発見するのに有効です.
この研究は,バイオシンセシスによるモロイドンベースの治療法の開発への道を開きます.

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