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在Aspergillus nidulans中的类平衡通过异构的烯合成酶表达方式揭示

Sung Chul Park¹, Breanne N Steffan¹, Fang Yun Lim^1,2

¹Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.

Science advances

|February 21, 2024

概括

在Aspergillus nidulans中,真菌人工染色体 (FAC) 的异质表达改变了烯生物合成,产生了新型化合物,并揭示了真菌代谢途径的洞察力.

科学领域:

生物化学生物化学
分子生物学分子生物学
菌类学菌类学是指菌类学.

背景情况:

丝状真菌是自然产品 (NP) 的丰富生产者,其中许多产品由于实验室表达的挑战而仍然没有特征.
在此之前,真菌人工染色体 (FAC) 已被用于真菌基因集群的异质表达,以发现新型NP.
研究真菌的二次新陈代谢对于识别新的生物活性化合物至关重要.

研究的目的:

探索FACs在改变宿主代谢途径的新应用,以发现天然产品.
为了研究表达一个 * 伪体虫破坏性 * FAC 在 * Aspergillus nidulans * 在生物合成的影响.
为了描述由改变的代谢途径产生的新的真菌衍生化合物.

主要方法:

异质表达一个 * 伪体虫破坏性 * FAC 在 * Aspergillus nidulans *.
使用分析技术,对野生型 *A. nidulans* 和 FAC 变变剂之间的化学配置进行比较分析.
基因操纵,包括删除FAC中的烯合成酶基因,以确认路径变化.

主要成果:

*P. destructans* FAC的异质表达显著改变了*A. nidulans*的内源性基生物合成途径.
在FAC转化剂中,烯和阿斯尼丁类化合物的产量增加,其中包括三种新型烯.
在转化剂中观察到,特征性的 *A. nidulans* 烯,austinol 的合成显著下降.
在FAC中删除一个烯合成酶基因成功地恢复了野生类型的化学特征.

结论:

FACs的异质表达可以重编程宿主代谢途径,为天然产品发现提供了一种新的策略.
这项研究为真菌烯合成提供了意想不到的见解,突出了烯和法纳西酸盐代谢之间的相互作用.
代谢中间体的变化比率可以导致不同的化合物类的产生,如尼杜和阿斯尼丁,以牺牲其他如奥斯醇.

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