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

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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.