2-アミノ-3-ヒドロキシクロペント-2-エノンの形成と自然産物バイオシンセシスの組み込みのための3つの酵素経路
Wenjun Zhang1, Megan L Bolla, Daniel Kahne
1Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of the American Chemical Society
|April 17, 2010
まとめ
研究者らは,Streptomyces aizunenesisの3つの酵素経路を特定し,モエノミシンなどの天然製品の重要な成分であるC(5) Nリングを形成しました. この経路は,凝縮,サイクル化,アミド結合のための特定の酵素を含み,天然製品生物合成の洞察を提供します.
科学分野:
- 微生物学 微生物学とは
- バイオケミストリー バイオケミストリー
- 自然製品化学 自然製品化学
背景:
- 多くの天然製品には,2-アミノ-3-ヒドロキシcyclopent-2-enone (C(5) N) リングがあり,ポリエノ酸のスキャフォールドと結びついています.
- バクテリアゲノム採掘は,3つのタンデムオープンリーディングフレーム (ORF) がC ((5) N形成と結合に関与する可能性を示唆しました.
研究 の 目的:
- C(5) N環系の生物合成経路を解明する.
- ECO-02301遺伝子クラスタの3つの特定のORF (ORF33-35) の酵素活性を特徴付ける.
主な方法:
- Escherichia coli.から再結合タンパク質を浄化する.
- サブストラット特異性と反応機構を決定するためのインビトロ酵素測定法.
- 5-アミノレブリン酸 (ALA) やALA-CoAなどの中間物質の特性.
- 自然基質を模倣するために合成アナログの使用.
主要な成果:
- PLPに依存する酵素であるORF34は,サクシニル-CoAとグリシンから5-アミノレブリン酸 (ALA) を合成する.
- アチル-CoAリガゼであるORF35は,ALAをALA-CoAに変換し,非酵素的サイクル化が容易である.
- また,ORF34は,ALA-CoAのC(5) Nリングへのサイクリングを触媒として作用します.
- ATPに依存するアミド合成酵素ORF33は,C(5) N環をポリエノ酸模倣に結合する.
結論:
- C(5) N リング形成と結合のための新しい3つの酵素経路が特徴付けられました.
- この経路は,専用のALA合成酵素,アシル-CoA結合酵素,およびアミド合成酵素を含み,モエノミシンを含む他の天然製品の生物合成において保存される可能性が高い.
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