Secondary metabolic gene cluster silencing in Aspergillus nidulans
Secondary metabolic gene cluster silencing in Aspergillus nidulans
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DOI：
10.1111/j.1365-2958.2006.05330.x
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Keller, Nancy P.
中科院分区：
文献类型：
--
作者：
Bok, Jin Woo;Noordermeer, Daan;Keller, Nancy P.
与大多数初级代谢基因相反，参与次级代谢和某些营养物质利用途径的基因在真菌中聚集。最近发现一种核蛋白LaeA是构巢曲霉中几个次级代谢产物基因簇转录所必需的。在这里，我们表明，LaeA调节不延伸到养分利用或spoC 1孢子形成集群。LaeA调控的次级代谢物簇之一包含致癌毒素杂色曲霉素（ST）生物合成所需的正调控基因（即aflR）和生物合成基因。ST基因簇表达的分析表明，LaeA调控的集群是位置特异性的，因为毗邻ST簇的基因的转录在Delta laeA突变体中不受影响，并且在ST簇中放置主要代谢基因argB导致Delta laeA背景中的argB沉默。当将afIR的额外拷贝置于簇外而不是置于簇中时，修复ST簇基因表达。位点特异性突变的S-腺苷甲硫氨酸（蛋氨酸）的结合位点在LaeA产生一个三角洲laeA的表型表明蛋白质是一个甲基转移酶。
In contrast to most primary metabolism genes, the genes involved in secondary metabolism and certain nutrient utilization pathways are clustered in fungi. Recently a nuclear protein, LaeA, was found to be required for the transcription of several secondary metabolite gene clusters in Aspergillus nidulans. Here we show that LaeA regulation does not extend to nutrient utilization or the spoC1 sporulation clusters. One of the secondary metabolite clusters regulated by LaeA contains the positive regulatory (i.e. aflR) and biosynthetic genes required for biosynthesis of sterigmatocystin (ST), a carcinogenic toxin. Analysis of ST gene cluster expression indicates LaeA regulation of the cluster is location specific as transcription of genes bordering the ST cluster are unaffected in a Delta laeA mutant and placement of a primary metabolic gene, argB, in the ST cluster resulted in argB silencing in the Delta laeA background. ST cluster gene expression was remediated when an additional copy of aflR was placed outside of the cluster but not when placed in the cluster. Site-specific mutation of an s-adenosyl methionine (AdoMet) binding site in LaeA generated a Delta laeA phenotype suggesting the protein to be a methyltransferase.