ベンゼニジオール・ラクトン・スキャフォールドの合成生物学的調整のためのO-メチル化の地域選択性の合理的な再プログラム
Xiaojing Wang1,2,3, Chen Wang1,2, Lixin Duan2,4
1Biotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
Journal of the American Chemical Society
|February 16, 2019
まとめ
新しいO-メチル化天然製品を作るために 合成されたO-メチルトランスファーゼ (OMT) を使用して 効率的な生体合成と生体触媒方法を開発しました これらのエンジニアリングされた酵素は,薬の発見と開発のために調整可能な地域選択性を提供します.
科学分野:
- 生物触媒と代謝工学
- 自然製品による薬物発見
- 酵素工学
背景:
- O- メチル化は,小分子天然製品の薬動学および薬動力学 (PK/ PD) 特性に大きな影響を及ぼします.
- 効率的なO-メチルトランスフェラーゼ (OMT) バイオカタリストは,基板の乱交性と調整可能な地域選択性を持つことが,薬剤の発見と開発に不可欠である.
- OMT触媒による合成には,スケーラブルで持続可能な生産方法が必要です.
研究 の 目的:
- 非天然のO-メチル化ポリケチドを生産するための効率的な生物合成および生物触媒プラットフォームを確立する.
- 構造誘導工学による OMT 地域選択性の再プログラミングを実証する.
- エンジニアリングによる地域選択性と基板の可塑性との関係を調査する.
主な方法:
- オートゴーナル地域特異性を持つキノコのOMTのペアを使用した.
- 酵素の地域選択性を修正するために,合理的,構造主導の活性サイト空洞工学を使用した.
- 生物合成と生物触媒の生産プラットフォームを開発しました.
主要な成果:
- 不自然なO-メチル化ベンゼンジオールラクトンポリケチドを成功裏に生成した.
- エンジニアリングされたOMTが再プログラムされた地域選択性を示すことが示されました.
- エンジニアリングされた地域選択性と基板の可塑性との相互作用を特徴づけた.
結論:
- エンジニアリングされたOMTは 薬物発見のための多様な化学物質を生成するための強力なツールです
- これらの生物触媒プラットフォームは,バイオアクティブ・スキャフォードの PK/PD最適化を促進します.
- この発見は,非自然な製品の合成生物学的調整を導くものです.
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