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通过工程化碳酸转移酶实现的固态分离性内分子环
Ajay L Chandgude1, Xinkun Ren1, Rudi Fasan1
1Department of Chemistry , University of Rochester , 120 Trustee Road , Rochester , New York 14627 , United States.
Journal of the American Chemical Society
|May 18, 2019
概括
工程化肌球蛋白生物催化剂进行不对称的分子内循环化,以产生有价值的循环化γ-乳. 这种新的生物催化方法可实现药物化学和天然产品合成的立体合成.
科学领域:
- 生物催化和酶工程
- 有机合成
- 医学化学
背景情况:
- 循环融合的γ-乳酸是许多生物活性分子中的关键结构动机.
- 这些化合物的高效和立体选择性合成仍然是有机化学的一个重大挑战.
研究的目的:
- 开发用于不对称的分子内循环化反应的工程化肌球蛋白生物催化剂.
- 在合成循环融合的γ-乳酸盐中实现高产量和反选择性.
- 通过蛋白质工程探索立体分离合成.
主要方法:
- 用肌球蛋白进行蛋白质工程,以制造新的生物催化剂.
- 不对称的分子内循环化基.
- 整个细胞的转化用于格拉姆尺度合成.
- 将环基-γ-乳制成三基替代环基.
主要成果:
- 工程化肌球蛋白有效地催化了高达99%的酶体过量.
- 蛋白质工程产生了具有立体差异性选择性的肌球蛋白变体.
- 实现了和天然产品的关键中间体的格拉姆尺度合成.
- 通过酶生成的乳被转化为纯环.
结论:
- 这项研究提供了第一个使用工程化肌球蛋白的生物催化性分子内循环化示例.
- 开发的策略为有价值的循环融合γ-乳的立体分离制备提供了一个有吸引力的途径.
- 这种生物催化方法对药物化学和天然产品合成有重大影响.
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