チオペプチドピリジン合成酵素 (TbtD) は分子間形式のアザ-ディエルス-アルダー反応を触媒とする

Jonathan W Bogart¹, Albert A Bowers¹

¹Division of Chemical Biology and Medicinal Chemistry Eshelman School of Pharmacy, and Lineberger Comprehensive Cancer Center , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27514 , United States.

Journal of the American Chemical Society

|January 18, 2019

まとめ

チオペプチド合成に不可欠なピリジン合成は,一般的な塩基触媒で活性化と基板耐性を示します. この発見により,多用途の生物触媒の可能性と2箇所の基板認識メカニズムが明らかになりました

科学分野:

生化学と酵素学
有機合成
自然製品の生物合成

背景:

チオペプチドピリジン合成は,複雑なチオペプチド抗生物質の生物合成における重要な酵素である.
これらの酵素は,チャレンジする分子内アザ- [4 + 2]サイクロアディションを触媒化し,三置換ピリジンコアを形成する.

研究の目的:

チオペプチドピリジン合成の触媒機構と基板耐性を調査する.
これらの酵素が合成用途の多用途生物触媒としての可能性を探求する.

主な方法:

ピリジン合成酵素の活性を評価するために,インビトロ酵素測定を行った.
酵素動力学と基質範囲に対する効果を研究するために,一般的塩基触媒を用いた.
特定のピリジン合成酵素であるTbtDの触媒的汎用性は,分子内および分子間反応の両方で評価されました.

主要な成果:

チオシリンとチオムラシン経路からのピリジン合成酵素の活性が,一般的な塩基触媒によって有意に増加した.
一般的な塩基触媒は,これらのピリジン合成の基板耐性を拡大した.
TbtDは,本来の分子内循環に加えて,分子間循環反応を行う能力を示した.

結論:

一般的な塩基触媒は,チオペプチドピリジン合成の活性と基板耐性を高める重要な要因である.
TbtDで示されるピリジン合成は,分子内および分子間反応の両方を行うことができる生物触媒として重要な汎用性を持っています.
発見は,ピリジン合成の2サイト基板認識モデルを支持し,基板の関与と処理に不可欠です.

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