在工厂底盘中生产埃托波介质的总生物合成
Journal of the American Chemical Society
|November 23, 2019
概括
研究人员对烟草植物进行了改造, 以产生 (-) - 脱氧菌毒素, 这是一种癌症药物的关键前体. 这种生物合成方法提供了一个可靠的替代方案,
科学领域:
- 植物生物技术
- 代谢工程
- 自然产品生物合成
背景情况:
- 乙胺是一种重要的植物化学疗法剂.
- 目前的化物生产依赖于喜马拉雅果的半合成, 面临供应链漏洞.
- 需要一种可靠,可扩展的以太前体生产方法.
研究的目的:
- 建立一种可靠的方法来制造 (-) - 脱氧基毒素,这是一种晚期的前体.
- 在烟草植物中设计一种生物合成途径,用于前体的生产.
- 克服与传统提取方法相关的局限性.
主要方法:
- 通过16个基因的短暂表达工程烟草植物.
- 嵌入的基因可供桃醇供应和埃托酸路由酶从果.
- 使用烟草作为多步生物合成途径的生产底盘.
主要成果:
- 在人工烟草叶中实现了毫克级的 (-) - 脱氧基毒素的产生.
- 累积的 (-) - 脱氧菌毒素最多为4.3mg/g干植物重量.
- 分离的高纯度 (-) - 脱氧菌毒素含量高达0.71 mg/g干植物重量.
结论:
- 已证明长生合成路径 (> 10 个步骤) 的有效转移到烟草生产系统.
- 建立了可行的毫克级总生物合成以获取有价值的化疗前体.
- 提供了一个可持续和可靠的替代品以化物前体生产.
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