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一种捕获释放策略,用于基因组驱动的发现抗增殖性功能化的捕获释放策略

Friedrich J Ehinger¹, Kirstin Scherlach¹, Felix Trottmann¹

¹Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), Beutenbergstraße 11a, 07745, Jena, Germany.

Angewandte Chemie (International ed. in English)

|December 16, 2024

概括

研究人员开发了一种新方法,在微生物中找到含的. 这种方法导致发现了具有显著抗癌细胞和线虫的抗增殖活性的新型环.

科学领域:

自然产品的发现自然产品的发现
化学生物学化学生物学
微生物生物技术微生物生物技术

背景情况:

富兰功能化具有显著的药理兴趣,因为它们的生物活性和生物结合的潜力.
具有毛侧链的自然存在的是罕见的,这限制了它们的研究和应用.
开发有效的方法来识别和生产这些化合物对于药物发现至关重要.

研究的目的:

开发一种精简的方法来预测和评估含有3-氨 (Fua) 的的微生物产量.
在各种细菌物种中发现新的含Fua和它们的生物合成途径.
为了描述新发现的Fua含有环的生物活性.

主要方法:

基因组挖掘结合可逆性,化学选择性标记毛残留物以进行质谱指导的识别.
使用根素Fua合成酶作为生物信息处理和Fua生物合成的异构复合.
适应捕获和释放策略,用于固相丰富的基替代.

主要成果:

在actinomycetes,蓝藻细菌,actinobacteria和γ-proteobacteria中确定了以前未知的Fua生物合成途径.
在本地生产者中检测到含有Fua的代谢物,使用可逆标记的代谢分析.
发现并描述了两种新的Fua环酸家族,即rubriamides和typhamides.
鲁布里亚米德和蒂法米德对人类瘤细胞和线虫有强大的抗增殖作用.

结论:

与之前的假设相反,含的在细菌中分布广泛.
开发的捕获释放策略与基因组挖掘相结合,对于发现新的替代天然产品是有效的.
新发现的rubriamides和typhamides代表了治疗开发的有希望的线索.

关键词:

循环类可以迪尔斯老年人的反应基因组采矿的研究非正规氨基酸非正规氨基酸反应性的侧链反应性侧链

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