プレペプチド遺伝子置換とバチルス・セレウスによるin vivo処理によるチオシリンリングサイズ変異の生成
Albert A Bowers1, Michael G Acker, Travis S Young
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA.
Journal of the American Chemical Society
|June 13, 2012
まとめ
バシルス・セレウスは,天然のシアゾリルペプチドであるチオシリンを産生する. 競争実験では,重要なサイクル化ステップが,新しい,多様なリングサイズを作り,天然製品の多様性を拡大することを明らかにしています.
科学分野:
- 自然製品バイオシンセシス 自然製品バイオシンセシス
- 微生物による二次代謝
- 化学生物学 化学生物学とは
背景:
- ティオシリンは,バシルス・セレウスによって生産されるチアゾリルペプチドです.
- バイオシンセシスは,前駆体ペプチドの翻訳後の改変を含みます.
- 重要なステップは,2つのセリン残基間の正式なサイクル添加であり,マクロサイクルを形成します.
研究 の 目的:
- ティオシリン生物合成における最終的なマクロサイクライゼーションステップの乱交性を調査する.
- 変化したサイクライゼーションによる変種リングサイズの生成を調査する.
- 天然シアゾリルペプチドの既知の構造的多様性を拡大する.
主な方法:
- サイクライゼーション反応を調査するために競争実験を活用しました.
- 分析された製品は,変異のリング構造を特定し,特徴づけます.
- バチルス・セレウスATCC 14579の生物合成を研究するために,遺伝的または生化学的アプローチを採用しました.
主要な成果:
- マクロサイクライゼーションのステップで有意な乱交が示された.
- リングサイズが変化したチオシリンのいくつかの変種を成功裏に生成し,特定しました.
- 天然のチオシリンで以前に報告されていないリングサイズが観察されました.
結論:
- ティオシリン生物合成における最終的なマクロサイクリングステップは,非常に柔軟です.
- この柔軟性により,様々なチアゾリルペプチド構造が自然に生成できます.
- この発見は,ユニークなリングアーキテクチャを持つ新しい天然製品を発見するための道を開きます.
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