線形アグリコンは,メチミシン生物合成におけるグリコシルトランスフェラーゼDesVIIの基質である:分析と含意
Chai-Lin Kao1, Svetlana A Borisova, Hak Joong Kim
1Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
Journal of the American Chemical Society
|April 28, 2006
まとめ
この研究は,マクロリドグリコシルトランスフェラーゼが,周期的だけでなく,線形ポリケチド前駆体を処理できることを示しています. これは,マクロリド抗生物質の生物合成経路の理解を拡大します.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 抗生物質の合成について
背景:
- マクロリド抗生物質は,ポリケチドアグリコンと砂糖を含む.
- アグリコンの合成はポリケチド合成酵素 (PKS) によって媒介され,グリコシルトランスフェラーゼによるグリコシル化が媒介されます.
- グラコシライゼーションは,アグリコンのサイクル化とPKSからの放出後に発生することが知られている.
研究 の 目的:
- マクロリドグリコシルトランスフェラーゼが,アシルキャリアタンパク質 (ACP) に結合した線形ポリケチド前駆体を処理できるかどうかを調査する.
- マクロライド抗生物質のバイオシンセシスの代替経路を探求する.
主な方法:
- 線形アグリコンの前駆体である10-デオキシメチノリドが,N-アセチルシステアミン (NAC) チオエステルとして化学合成される.
- 合成された前駆体をTDP-d-デソサミン,グリコシルトランスフェラーゼDesVII,アクティベーターDesVIIIでインキュベーションする.
- 高解像度質量スペクトロメトリを用いた反応製品の分析.
主要な成果:
- 線形前駆物のグリコシル化と一致するより極性な製品が生成されました.
- グリコシルトランスフェラーゼDesVIIは,線形10-デオキシメチノリド前駆体を成功裏に処理した.
- この処理は,サイクル基板と比較して,減少した,しかし測定可能な活性で発生しました.
結論:
- マクロライドグリコシルトランスフェラーゼは,線形ポリケチド前駆体を認識し,グリコシル化することができます.
- この発見は,マクロリド生物合成におけるグリコシルトランスファーゼの既知の基板特異性を拡大する.
- この研究は,マクロリド抗生物質の組み立て経路の柔軟性に関する新しい洞察を提供します.
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