プラテンシミシン生物合成におけるエーテル形成を誘発するサイトクロームP450触媒化水酸化
Jeffrey D Rudolf1, Liao-Bin Dong1, Xiao Zhang1
1Department of Chemistry , The Scripps Research Institute , Jupiter , Florida 33458 , United States.
Journal of the American Chemical Society
|September 15, 2018
まとめ
プラテンシミシン (PTM) は,効力のためにユニークなエーテル結合を使用します. この研究は,PtmO5酵素が
科学分野:
- 自然製品の生物合成
- 酵素学
- 有機化学
背景:
- プラテンシミシン (PTM) とプラテンシン (PTN) は脂肪酸合成酵素を抑制する天然産物である.
- PTMの効能と選択性は,PTNで見つからないユニークなエーテル部分と関連しています.
- 以前の研究では,PtmT3がディターペン合成体として特定され,PtmO5がエーテル形成に関与していた.
研究 の 目的:
- プラテンシミシン生物合成におけるエーテル分子の形成の酵素的メカニズムを解明する.
- この過程におけるサイトクロームP450酵素PtmO5の役割について説明する.
主な方法:
- PtmO5酵素のインビトロ特性
- PtmO5の基質特異性と反応産物の分析
- 水酸化とエーテル形成のステレオ化学の決定
主要な成果:
- PtmO5は,エンタカウラン基板のC-11位置をステレオ選択的に水酸化する.
- この水酸化により11S,16R-ダイオルの中間産物が生成される.
- PTMのエーテル分子は,この二酸化物の中間物質の循環により,C-11の水酸化による酸素によって形成される.
結論:
- PtmO5は,PTMのエーテル部分に不可欠なステレオ選択C-11水酸化を触媒する重要な酵素である.
- この研究は,天然製品の生物合成における新しいエーテル形成経路に関する詳細なメカニズム的な洞察を提供します.
- この経路を理解すると,新しい脂肪酸合成阻害剤の設計に役立つ.
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