结构不可知生物活性驱动的组合生物合成揭示了新的抗糖尿病和抗癌三聚胺
Yong Zhao1, Yao-Tao Duan1, Jie Zang2
1Biochemical Engineering Group, Department of Plant and Environment Sciences, Faculty of Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark.
Angewandte Chemie (International ed. in English)
|September 19, 2024
概括
这项研究引入了用于组合生物合成的生物活性导向工作流,加速了发现有力的天然产品候选药物的过程. 该方法有效地识别出有前途的酶组合,用于生产像三烯酸这样的生物活性分子.
科学领域:
- 自然产品化学 自然产品化学
- 合成生物学 合成生物学
- 药物发现 药物发现 药物发现
背景情况:
- 组合生物合成扩大了自然产品的多样性,但受到复杂化合物隔离和表征的阻碍.
- 在隔离之前分析代谢物生物活性对于有效的选和优化至关重要.
研究的目的:
- 为组合生物合成开发和演示一种结构不可知,生物活性驱动的工作流.
- 为了加快强大的生物活性天然产品的识别,特别是针对PTP1B的三类药物.
主要方法:
- 实施了以生物活性查为指导的代组合生物合成方法.
- 应用工作流来生成三烯酸并评估它们对PTP1B的抑制活性.
主要成果:
- 通过使用生物活性引导工作流程,成功地将1000多个潜在组合缩小到五个非常强大的候选人.
- 确定了20种不同的三类化合物,包括四种新型化合物和一种混合物,作为强大的PTP1B抑制剂.
结论:
- 生物活性驱动的工作流显著加快了组合生物合成中的命中标识.
- 这一策略广泛适用于发现新生物活性天然产品以加速药物发现.
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