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神秘的皮佩拉衍生物通过敲除阿斯伯吉勒斯黄菌中的全球调节器LaeA来激活

Yaping Liu¹, Pengkun Li¹, Changxing Qi¹

¹Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.

Bioorganic & medicinal chemistry

|March 19, 2024

概括

在Aspergillus flavipes中禁用flLaeA调节器解锁了隐藏的二次代谢物. 这种遗传方法产生了新型化合物,flavipamides A和B,为真菌天然产品的发现提供了新的途径.

科学领域:

微生物学微生物学
自然产品化学自然产品化学
基因组学就是基因组学.

背景情况:

菌,特别是阿斯伯吉勒斯菌种,是多样化二次代谢产物的丰富生产者.
许多真菌的二次代谢物生物合成基因集群在标准实验室条件下保持沉默或"隐秘".
全球调节器LaeA在控制Aspergillus中的二次新陈代谢方面发挥着至关重要的作用.

研究的目的:

为了激活Aspergillus flavipes中神秘的二次代谢物生产.
为了识别和描述来自A. flavipes. 的新化合物.
探索全球调节器失活的实用性,用于天然产品的发现.

主要方法:

基因组测序的Aspergillus flavipes. . . 的基因组测序.
全球调节器flLaeA的基因淘汰.
扩大 ΔflLaeA 突变菌株的发酵.
化合物的LC-MS引导隔离和净化.
光谱分析 (NMR,MS) 和电子圆形二元化 (ECD) 用于结构阐明.
生物信息分析和13C同位素标记用于生物合成途径的阐明.

主要成果:

flLaeA的非激活导致两个NRPS类生物合成基因集群的上调调节.
他们分离了五种化合物,包括两种新的皮佩拉衍生物,弗拉维帕米德A和B.
使用光谱数据和ECD计算,确定了flavipamides A和B的结构.
基于生物信息学和同位素标记数据,提出了新化合物的生物合成途径.

结论:

全球调节器LaeA的无活化是一种有效的策略,可以访问Aspergillus flavipes中的神秘的二次代谢物.
这项研究报告了首次使用LaeA无活化来发现真菌天然产品的实例.
这些发现提供了一种新的基因操纵方法,用于从真菌中发现新的二次代谢产物.

关键词:

亚斯伯吉勒斯黄虫 (Aspergillus flavipes) 是一种植物.这是神秘的,神秘的.基因集群是一种基因集群.这就是LC-MS.拉伊亚是一个很好的地方.皮佩拉津 (Piperazine) 是一种药物.

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