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相关实验视频

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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes T&#252;6028
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聚基合成的化学信息指导工程

Amin Zargar1,2,3, Ravi Lal1,2, Luis Valencia1,2

  • 1Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, California 94608, United States.

Journal of the American Chemical Society
|May 16, 2020
PubMed
概括

化学信息学通过指导还原循环 (RL) 交换来帮助聚基合成酶 (PKS) 工程. 这一战略成功地产生了高度的短链脂肪酸和三酸乳,从而创造了新的化学产品.

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科学领域:

  • 生物技术
  • 合成生物学
  • 化学工程

背景情况:

  • 聚基合成酶 (PKS) 对于产生多种分子至关重要.
  • 工程PKS模块,特别是通过还原循环 (RL) 交换和β-碳的生产,是一个重大挑战.
  • 通常用于药物发现的化学信息学尚未广泛应用于PKS工程.

研究的目的:

  • 建立化学信息学作为PKS减少循环 (RL) 交换的可行策略.
  • 证明RL交换对于产生新化学产品的有用性.
  • 将化学结构的相似性与工程PKS系统的生产产量相关联.

主要方法:

  • 将多种捐赠RL引入利波素PKS (LipPKS1) 的第一个扩展模块.
  • 通过将RLs引入LipPKS2用于三酸乳生产,将该方法扩展到双模块通信.
  • 使用原子对化学相似性分析来预测和与产品形成相关.

主要成果:

  • 工程化单模PKS的产品标位与RL基底相似,与LipPKS1相对应.
  • 使用工程*Streptomyces albus* J1074达到165mg/L的短链脂肪酸.
  • 在单模和双模PKS工程中观察到原子对化学相似性和产品产量之间的统计学显著相关性.

结论:

  • 化学信息学提供了一种强大且可预测的方法来设计PKS减速循环 (RL) 交换.
  • 这种方法有助于生产所需的非自然聚化物产品.
  • 已建立的化学信息方法可以指导PKS的合理设计,用于新型化学合成.