エポチロン生物合成におけるシス二重結合形成のメカニズムを解明する
Li Tang1, Shannon Ward, Loleta Chung
1Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, California 94545, USA. tang@kosan.com
Journal of the American Chemical Society
|January 8, 2004
まとめ
ポリケチド合成酵素 (PKS) 複合体はエポチロンDとCを生成する.脱水酵素ドメイン5 (DH5) は,これらの化合物における12,13-cis-二重結合の形成に不可欠である.
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.
- 自然製品合成 自然製品合成
背景:
- エポチロンは,Sorangium cellulosumから分離されたマクロサイクル化合物です.
- それらは,モジュラーポリケチド合成酵素 (PKS) 酵素複合体によって合成されます.
- エポチロンDとCは,12,13-cis-二重結合を持つ最後の前半の中間物質である.
研究 の 目的:
- エポチロン生物合成における12,13-cis-二重結合形成のメカニズムを調査する.
- 12,13-cis-二重結合を生成する特定の酵素ドメインを特定する.
- エポチロン合成におけるモジュール5 (DH5) の脱水酵素 (DH) ドメインの役割を明らかにする.
主な方法:
- Sorangium cellulosumのPKS遺伝子クラスタの遺伝子操作について.
- 改変株によって生産されたエポチロン中間物の分析.
- 酵素ドメインとその活動の生化学的特徴.
主要な成果:
- PKSのモジュール4には脱水酵素ドメインがないが,12・13二重結合の形成に関与している.
- モジュール5 (DH5) のDHドメインの不活性化により10,11-デヒドロ-13-ヒドロキシエポチロンDが生成されました.
- これは12,13-脱水ステップにDH5が必要であることを確認しています.
結論:
- デヒドレーターゼドメイン5 (DH5) は,エポチロンにおける12,13-cis-二重結合の形成に重要な役割を果たします.
- ドメインスキップとモジュラー・スタッティングを含む機械的モデルは,DH5の繰り返し活動を説明する.
- このメカニズムを理解することで,複雑な自然産物の生物合成の洞察が得られます.
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