Role of VeA-Dependent Genes and Proteins in Mycotoxin Production and Development

性状（由申请方提供）：曲霉属。霉菌毒素感染玉米、棉花、高粱和坚果。控制真菌毒素的生物合成或真菌的发展将减少其破坏性的健康和经济影响。由于信号通路在曲霉属中趋于保守，因此使用构巢曲霉模型系统来研究真菌毒素产生和形态发育的调节。曲霉属产生抗性结构：黄曲霉和寄生曲霉中的菌核和A. nidulans。对闭囊壳或菌核发育控制的分子研究是有限的。只有少数调控基因是已知的。我们发现veA基因的缺失阻断了霉菌毒素的产生以及A. nidulans，A. flavus和A.寄生虫我们还发现，形态发育和次生代谢也控制了跨属的全球调节器。VeA蛋白是一种真菌特异性的有希望的控制策略的目标，但是，它不存在同源性，以前描述的蛋白质。我们先前的AREA资助的主要目标是进一步描述VeA控制真菌毒素生物合成和形态发生的调控机制，在模型系统中，A。nidulans。为此，我们已经a）鉴定了VeA相互作用蛋白，和B）在缺失的veA菌株中获得了几个抑制突变体，用于鉴定涉及真菌毒素产生的veA下游的遗传元件。我们成功地实现了这些目标。根据蛋白质组学方法，我们已经确定了VeA相互作用蛋白。此外，我们的诱变方法，根据先前的目标2应用，导致几个回复突变体，其中两个完全表征，概述了在以前的区域补助金。 在目前的区域，我们提出：目标1：表征新的VeA相互作用的蛋白质，和目标2：表征回复突变体和基因的影响所造成的突变。由于跨物种真菌调控网络的保守性和VeA仅在真菌中发现的事实，涉及VeA的控制策略可能对曲霉属真菌毒素污染有效。以及其他植物和动物病原体。 公共卫生相关性：这是对先前关于VeA作用机制的AREA资助研究的更新，VeA是一种真菌全球调节剂，可控制次级代谢产物的生物合成，如强效致癌真菌毒素以及真菌发育。事实上，VeA是真菌所独有的，并且在许多真菌中是保守的，这使得VeA成为控制真菌病原体和构成重要健康威胁的有害真菌毒素的产生的有价值的可能靶标。

DESCRIPTION (provided by applicant): Aspergillus spp. mycotoxins infect corn, cotton, sorghum and nuts. Controlling mycotoxin biosynthesis or fungal development would decrease its devastating health and economic impact. Because signaling pathways tend to be conserved in Aspergillus spp, the model system Aspergillus nidulans is used to study regulation of mycotoxin production and morphological development. Aspergillus spp. produce resistant structures: sclerotia in Aspergillus flavus and Aspergillus parasiticus and fruiting bodies called cleistothecia in A. nidulans. Molecular studies over the control of cleistothecial or sclerotial development are limited. Only a few regulatory genes are known. We found that deletion of the veA gene blocks mycotoxin production as well as the formation of resistant structures in A. nidulans, A. flavus and A. parasiticus. We also found that morphological development and secondary metabolism is also controlled by this global regulator across genera. The VeA protein is a fungal-specific promising target for a control strategy; however, it does not present homology to previously described proteins. The main goal of our previous AREA grant was to further characterize the regulatory mechanism through which VeA controls mycotoxin biosynthesis and morphogenesis, in the model system, A. nidulans. For that we have a) Identified VeA interacting proteins, and b) obtained several suppressor mutants in a deletion veA strain for the identification of the genetic elements downstream from veA involved in mycotoxin production. We successfully carried out these objectives. Following a proteomics approach we have identified VeA-interacting proteins. Also our mutagenesis approach, applied according to the previous aim 2, resulted in several revertant mutants, two of them are fully characterized as outlined in the previous AREA grant. In the current AREA we propose: Aim1: to characterize novel VeA interacting proteins, and Aim 2: to characterize revertant mutants and the genes affected by the inflicted mutations. Because of the conserved nature of fungal regulatory networks across species and the fact that VeA has only been found in fungi, a control strategy involving VeA may be effective against mycotoxin contamination by Aspergillus spp. and against other plant and animal pathogens. PUBLIC HEALTH RELEVANCE: This is a renewal of a previous AREA grant study on the mechanism of action of VeA, a fungal global regulator that controls the biosynthesis of secondary metabolites, such as potent carcinogenic mycotoxins, as well as fungal development. The fact that VeA is unique to fungi and it is conserved in many fungi, makes VeA a valuable possible target to control fungal pathogens and the production of deleterious mycotoxins that constitute an important health threat.