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Chemical Triphosphorylation of Oligonucleotides
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フォスフォナート・フォスフォノトリキシンの完全な生物合成経路: 2つの異なるチアミン二酸化物依存酵素がC−C結合を形成するために作業を分割する
Yuxun Zhu1, Taro Shiraishi1, Jianwen Lin1
1Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Journal of the American Chemical Society
|September 6, 2022
まとめ
研究者は,除草剤のフォスフォノトリキシン (PTX) の完全な生物合成を解明しました. TPPに依存する2つの酵素は 重要な炭素-炭素結合を形成するために 独特に協力し,前例のない天然製品の生物合成戦略を明らかにします
科学分野:
- 自然製品の生物合成
- 酵素学
- 化学生物学
背景:
- リン酸塩は生物学的リン酸塩と炭酸塩を模倣し,しばしば生物学的活性を示します.
- サッカロトリックス (Saccharothrix) spによって生成されるフォスフォナートであるフォスフォノトリキシン (PTX). ST-888は除草剤である
- PTXのバイオシンセシスを理解することは,その応用と関連する天然製品を探求するための鍵です.
研究 の 目的:
- フォスフォノトリキシン (PTX) の完全な生物合成経路を解明する.
- 酵素メカニズムを研究するために,PTX生物合成を in vitro で再構成する.
- PTX 生成に関与する重要な酵素と新しいC-C結合形成戦略を特定する.
主な方法:
- 提案されたPTX生物合成経路の in vitro 再構成.
- 個々の酵素の機能を特徴づけるための酵素分析.
- 先進的な分析技術を用いた反応中間産物と産物の分析
主要な成果:
- 2つの脱水酵素は,フォスフォノピルーバート (PnPy) を2ヒドロキシ3フォスフォノプロパノ酸 (HPPA) に還元することが示された.
- 4つの酵素がHPPAを (3-ヒドロキシ-2-オキシプロピル) リン酸 (HOPA) に変換することを特定した.
- スプリット遺伝子トランスケトラーゼホモログ (PtxB5/6) とアセトヒドロキシ酸シンタゼホモログ (PtxB7) は,ユニークなC-C結合形成によってPTXを形成する.
結論:
- この研究は,PTXの完全な in vitro 生合成経路を示しています.
- アセチルグループ移転の作業を分割する2つの異なるチアミン二酸化物 (TPP) 依存酵素を含む新しい生物合成戦略が明らかにされました.
- この研究は,天然製品の生物合成における前例のないC−C結合形成のメカニズムを強調しています.
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