LaeA negatively regulates dothistromin production in the pine needle pathogen Dothistroma septosporum
LaeA negatively regulates dothistromin production in the pine needle pathogen Dothistroma septosporum
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DOI：
10.1016/j.fgb.2016.11.001
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发表时间：
2016-12-01
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;Bradshaw, Rosie E.
在丝状真菌中，途径特异性和全局调节因子都调节参与次级代谢产物生物合成的基因。LaeA是一种全局调节剂，其因其突变表型而命名，即由于其对曲霉属中黄曲霉毒素途径调节剂AflR的作用而导致aflR表达丧失。松针病原体Dothistroma septosporum产生聚酮毒力因子dothistromin，其与黄曲霉毒素化学相关，并且其途径基因也由AflR的直系同源物调节。然而，dothistromin生物合成是独特的，因为它是在早期（而不是晚期）指数生长期打开，基因分散在一条染色体上的六个基因座中，而不是聚集在一起。因此，确定全局调节子LaeA的功能在D.隔孢菌为了解决这个问题，我们鉴定了一个LaeA直系同源物（DsLaeA），并在D.隔孢菌与曲霉属的黄曲霉毒素生产相反，DsLaeA的缺失导致dothistromin产生的增强和途径调节基因DsAflR的表达的增加。虽然其他推测的次级代谢产物基因在D.尽管隔孢霉对DsLaeA功能丧失表现出一系列不同的反应，但薄层色谱显示DsLaeA突变体中先前未知的代谢物水平增加。此外，这些突变体表现出减少无性孢子形成，发芽和疏水性。我们的数据表明，虽然DsLaeA的发育调控作用是保守的，但它在调节次生代谢中的作用不同于A. nidulans和似乎是物种特异性。这项研究提供了一个步骤，了解基本的差异，在调控的集群和片段组的次级代谢物基因，可能有助于了解功能适应次级代谢。(C)2016 Elsevier Inc. All rights reserved.
In filamentous fungi both pathway-specific and global regulators regulate genes involved in the biosynthesis of secondary metabolites. LaeA is a global regulator that was named for its mutant phenotype, loss of aflR expression, due to its effect on the aflatoxin-pathway regulator AflR in Aspergillus spp. The pine needle pathogen Dothistroma septosporum produces a polyketide virulence factor, dothistromin, that is chemically related to aflatoxin and whose pathway genes are also regulated by an ortholog of AflR. However, dothistromin biosynthesis is distinctive because it is switched on during early (rather than late) exponential growth phase and the genes are dispersed in six loci across one chromosome instead of being clustered. It was therefore of interest to determine whether the function of the global regulator LaeA is conserved in D. septosporum. To address this question, a LaeA ortholog (DsLaeA) was identified and its function analyzed in D. septosporum. In contrast to aflatoxin production in Aspergillus spp., deletion of DsLaeA resulted in enhanced dothistromin production and increased expression of the pathway regulatory gene DsAflR. Although expression of other putative secondary metabolite genes in D. septosporum showed a range of different responses to loss of DsLaeA function, thin layer chromatography revealed increased levels of a previously unknown metabolite in DsLaeA mutants. In addition, these mutants exhibited reduced asexual sporulation, germination and hydrophobicity. Our data suggest that although the developmental regulatory role of DsLaeA is conserved, its role in the regulation of secondary metabolism differs from that of LaeA in A. nidulans and appears to be species specific. This study provides a step towards understanding fundamental differences in regulation of clustered and fragmented groups of secondary metabolite genes that may shed light on understanding functional adaptation in secondary metabolism. (C) 2016 Elsevier Inc. All rights reserved.