α 分岐有機酸の生産のための経路の発見と工学
Michael R Blaisse1, Hongjun Dong1, Beverly Fu1
1Department of Chemistry, University of California, Berkeley , Berkeley, California 94720-1460, United States.
Journal of the American Chemical Society
|October 10, 2017
まとめ
研究者らは,アスカリス・スウムから得られた新型のチオラゼ-ケトレデクタゼペアを使用して,分岐酸を生成する微生物株を設計した. この突破は 価値あるα-分岐化合物の 生物学的合成能力を拡大します
科学分野:
- バイオテクノロジー
- 合成生物学
- 生物化学
背景:
- 細胞ベースの合成は 発酵を通じて再生可能な資源から小分子生産を可能にします
- 酵素による炭素-炭素結合形成サイクルは,モジュール生物合成に不可欠ですが,基板の制限に直面しています.
- ティオラーゼ酵素は合成を開始するが,複雑な分子の基板の多様性は限られている.
研究 の 目的:
- 枝分かれしたカルボキシル酸を生成する新しい酵素を特定し,特徴づけること.
- α-メチル分岐化合物の効率的な生物合成のための微生物システムを設計する.
- チオラゼベースの合成経路の基板範囲を拡大する.
主な方法:
- Ascaris suumのチオラゼ-ケトレデクタゼ酵素ペアの識別と生化学的特徴.
- エシェリキア・コライ菌株を分岐酸の生産に用いる技術
- 酵素活性と経路の選択性のin vitroおよびin vivo分析
主要な成果:
- 新しいチオラゼ-ケトレデクタゼペアはプロピオニル-CoAを使用して選択的にα-メチル分岐酸を生成する.
- エンジニアリングされたE. coliはキラル-2-メチル-3-ヒドロキシ酸 (1.1g L−1) と分岐エノ酸 (1.12g L−1) を生成した.
- ケトレデクタゼの活性が,α- 枝の選択性の主要な決定因子として特定された.
結論:
- 特定された酵素は,チオラゼベースの生物合成経路の有用性を拡張します.
- この研究は,ポリマーと化学前体のためのα-分岐化合物の生合成経路を提供します.
- 微生物の遺伝子組み換え株は 有益な分岐分子を 効率的に生成します
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