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柔性酶支持的类生物合成
Steven R Fleming1, Tessa E Bartges2, Alexander A Vinogradov3,4
1Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , United States.
Journal of the American Chemical Society
|January 3, 2019
概括
研究人员开发了一种基板生物合成方法,用于创建类基架,使得在不需要复杂的酶复合的情况下研究新类同类物和类合成物.
科学领域:
- 自然产品生物合成
- 合成生物学
- 医学化学
背景情况:
- 硫是一种通过广泛的翻译后修改从短衍生出的天然抗生素.
- 由于复制多酶通路的困难,研究硫生物合成,特别是合成酶在形成宏循环核中的作用是具有挑战性的.
- 目前研究酶的方法往往复杂且资源密集.
研究的目的:
- 开发一种可访问的基基生物合成策略.
- 克服与复制多种酶在硫路径相关的挑战.
- 为了研究和验证新的合成酶和生产新的类.
主要方法:
- 结合精选的RiPP (核糖体合成和转化后修饰的) 酶与细胞自由表达系统.
- 使用基于柔性酶的编码重新编程来促进生物合成.
- 开发了一种简化系统用于基的生产和酶活性验证.
主要成果:
- 成功建立了一种生产基架的基板生物合成方法.
- 获得了新的类同类的分析量.
- 证明了该策略在没有先前途径复制的情况下验证新的胺合成的实用性.
结论:
- 开发的无细胞生物合成策略简化了对酶的研究.
- 这种方法为发现和表征新天然产品及其生物合成机制提供了强大的工具.
- 该方法可简化对酶功能,特别是胺合成酶的验证.
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