Breaking the Silence: Protein Stabilization Uncovers Silenced Biosynthetic Gene Clusters in the Fungus Aspergillus nidulans
Breaking the Silence: Protein Stabilization Uncovers Silenced Biosynthetic Gene Clusters in the Fungus Aspergillus nidulans
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DOI：
10.1128/aem.01808-12
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发表时间：
2012-12-01
影响因子：
4.4
通讯作者：
Braus, Gerhard H.
中科院分区：
文献类型：
--
作者：
Gerke, Jennifer;Bayram, Oezguer;Braus, Gerhard H.
丝状真菌的基因组包含许多假定的基因簇，这些基因簇编码化学和结构多样化的次生代谢物（SMs）的生物合成，这些基因簇很少在实验室条件下表达。以前激活这些基因的方法主要是基于人工靶向细胞蛋白质合成装置。在这里，我们采用了另一种方法，通过删除COP9信号体中保守的真核csnE/CSN5去eddylase亚基，对模式真菌细粒曲霉的蛋白质降解装置进行遗传损伤。这种蛋白质降解缺陷导致先前沉默的基因簇的激活，该基因簇包括产生抗生素2,4-二羟基-3-甲基-6-（2-氧丙基）苯甲醛（DHMBA）的聚酮合成酶基因。csnE/CSN5基因在真菌中高度保守，因此，缺失是鉴定新SMs的可行方法。
The genomes of filamentous fungi comprise numerous putative gene clusters coding for the biosynthesis of chemically and structurally diverse secondary metabolites (SMs), which are rarely expressed under laboratory conditions. Previous approaches to activate these genes were based primarily on artificially targeting the cellular protein synthesis apparatus. Here, we applied an alternative approach of genetically impairing the protein degradation apparatus of the model fungus Aspergillus nidulans by deleting the conserved eukaryotic csnE/CSN5 deneddylase subunit of the COP9 signalosome. This defect in protein degradation results in the activation of a previously silenced gene cluster comprising a polyketide synthase gene producing the antibiotic 2,4-dihydroxy-3-methyl-6-(2-oxopropyl) benzaldehyde (DHMBA). The csnE/CSN5 gene is highly conserved in fungi, and therefore, the deletion is a feasible approach for the identification of new SMs.