Dothistromin genes at multiple separate loci are regulated by AflR
Dothistromin genes at multiple separate loci are regulated by AflR
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DOI：
10.1016/j.fgb.2012.11.006
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发表时间：
2013-02-01
影响因子：
3
通讯作者：
Bradshaw, Rosie E.
中科院分区：
文献类型：
--
作者：
Chettri, Pranav;Ehrlich, Kenneth C.;Bradshaw, Rosie E.
在真菌中，参与次生代谢物产生的基因通常聚集在一个位置。也有一些例外，比如合成曲曲霉素所需的基因，曲曲霉素是一种毒素，是黄曲霉毒素前体花青素a的化学类似物，由松针病原体Dothistroma septosporum产生。septosporum基因组序列的可用性可以鉴定推测的dothistromin基因，包括黄曲霉毒素调节基因AflR的同源物，并揭示了大多数基因分布在12号染色体上的6个独立区域（位点）（1.3 Mb）。在这里，我们表明了广泛分布的基因在d.s septosporum中的表达水平与基因位置（相对于它们与端粒的距离）无关，但AflR调节它们。敲除AflR基因的D. septosporum （Delta DsAflR）产生的消硫霉素急剧减少，但仍可检测到。这与曲霉种中缺乏黄曲霉毒素产生的同源Delta AflR突变体相反。Delta DsAflR突变体的表达模式有助于预测与降硫胺产生相关的全套基因。这包括一个短链芳基醇脱氢酶（NorB），它位于第11染色体而不是第12染色体上，但在Delta DsAflR中被下调24倍。在与番茄密切相关的病原菌黄枝孢子菌（Cladosporium fulvum）中发现了一组同源的降硫霉素基因，其组织结构与septosporum中的片段簇排列相似，尽管黄枝孢子菌不产生降硫霉素。在C fulvum中，关键生物合成基因的假原化解释了多巴胺缺乏的原因。去硫istromin基因的碎片化排列提供了一个协调控制分散的次级代谢物基因的例子；它还提供了一个例子，即减少抗甲状腺素的产生可能允许适应一种新的致病生活方式。(C) 2012爱思唯尔公司版权所有。
In fungi, genes involved in the production of secondary metabolites are generally clustered at one location. There are some exceptions, such as genes required for synthesis of dothistromin, a toxin that is a chemical analog of the aflatoxin precursor versicolorin A and made by the pine needle pathogen Dothistroma septosporum. The availability of the D. septosporum genome sequence enabled identification of putative dothistromin genes, including an ortholog of the aflatoxin regulatory gene AflR, and revealed that most of the genes are spread over six separate regions (loci) on chromosome 12 (1.3 Mb). Here we show that levels of expression of the widely dispersed genes in D. septosporum are not correlated with gene location with respect to their distance from a telomere, but that AflR regulates them. The production of dothistromin by D. septosporum in which the AflR gene was knocked out (Delta DsAflR) was drastically reduced, but still detectable. This is in contrast to orthologous Delta AflR mutants in Aspergillus species that lack any aflatoxin production. Expression patterns in Delta DsAflR mutants helped to predict the complete set of genes involved in dothistromin production. This included a short-chain aryl alcohol dehydrogenase (NorB), which is located on chromosome 11 rather than chromosome 12, but was 24-fold down regulated in Delta DsAflR. An orthologous set of dothistromin genes, organized in a similar fragmented cluster arrangement to that seen in D. septosporum, was found in the closely related tomato pathogen Cladosporium fulvum even though this species does not produce dothistromin. In C fulvum, pseudogenization of key biosynthetic genes explains the lack of dothistromin production. The fragmented arrangement of dothistromin genes provides an example of coordinated control of a dispersed set of secondary metabolite genes; it also provides an example where loss of dothistromin production might have allowed adaptation to a new pathogenic lifestyle. (C) 2012 Elsevier Inc. All rights reserved.