The putative C2H2 transcription factor MtfA is a novel regulator of secondary metabolism and morphogenesis in Aspergillus nidulans.
The putative C2H2 transcription factor MtfA is a novel regulator of secondary metabolism and morphogenesis in Aspergillus nidulans.
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DOI：
10.1371/journal.pone.0074122
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Calvo AM
中科院分区：
文献类型：
--
作者：
Ramamoorthy V;Dhingra S;Kincaid A;Shantappa S;Feng X;Calvo AM
模式真菌Nidulans的次生代谢是由保守的全球调控因子Vea控制的，Vea也控制着形态分化。在VEA调节的次生代谢物中，有真菌毒素杂色曲霉毒素(ST)。VEA的存在对于这种致癌化合物的生物合成是必要的。我们鉴定了一个能够在没有VEA的情况下合成ST中间体的突变株。该点突变发生在编码一种新的C2H2锌指结构域转录因子的基因的编码区，我们命名为MTFA。根瘤拟青霉MTFA基因产物定位于细胞核，与光照条件无关。在没有Vea的情况下，MTFA基因的缺失可以恢复霉菌毒素的生物合成，但当MTFA基因的表达通过缺失或过表达而改变时，具有Vea野生型等位基因的弧菌菌株的霉菌毒素产量显著减少。我们的研究表明，MTFA通过影响特异性ST基因簇激活物aflR的表达来调节ST的产生。重要的是，MTFA也是其他次生代谢基因簇的调节者，例如负责合成特鲁二酮和青霉素的基因。与ST的情况一样，MTFA的缺失或过表达也不利于Terquinone基因的表达。MTFA的缺失也降低了青霉素基因簇中基因的表达，从而减少了青霉素的产量。然而，在这种情况下，MTFA的过表达增强了青霉素基因的转录，使青霉素产量增加了5倍以上。重要的是，除了对次生代谢的影响外，MTFA还影响网纹夜蛾的无性和有性发育。MTFA的缺失会导致分生孢子和性阶段的减少。我们发现MTFA推测的同源基因在其他真菌物种中也是保守的。
Secondary metabolism in the model fungus Aspergillus nidulans is controlled by the conserved global regulator VeA, which also governs morphological differentiation. Among the secondary metabolites regulated by VeA is the mycotoxin sterigmatocystin (ST). The presence of VeA is necessary for the biosynthesis of this carcinogenic compound. We identified a revertant mutant able to synthesize ST intermediates in the absence of VeA. The point mutation occurred at the coding region of a gene encoding a novel putative C2H2 zinc finger domain transcription factor that we denominated mtfA. The A. nidulans mtfA gene product localizes at nuclei independently of the illumination regime. Deletion of the mtfA gene restores mycotoxin biosynthesis in the absence of veA, but drastically reduced mycotoxin production when mtfA gene expression was altered, by deletion or overexpression, in A. nidulans strains with a veA wild-type allele. Our study revealed that mtfA regulates ST production by affecting the expression of the specific ST gene cluster activator aflR. Importantly, mtfA is also a regulator of other secondary metabolism gene clusters, such as genes responsible for the synthesis of terrequinone and penicillin. As in the case of ST, deletion or overexpression of mtfA was also detrimental for the expression of terrequinone genes. Deletion of mtfA also decreased the expression of the genes in the penicillin gene cluster, reducing penicillin production. However, in this case, over-expression of mtfA enhanced the transcription of penicillin genes, increasing penicillin production more than 5 fold with respect to the control. Importantly, in addition to its effect on secondary metabolism, mtfA also affects asexual and sexual development in A. nidulans. Deletion of mtfA results in a reduction of conidiation and sexual stage. We found mtfA putative orthologs conserved in other fungal species.
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影响因子：
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作者：
Dhingra, Sourabh;Andes, David;Calvo, Ana M.
通讯作者：
Calvo, Ana M.
影响因子：
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通讯作者：
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作者：
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