Screening of chemical libraries in search of inhibitors of aflatoxin biosynthesis
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Aspergillus nidulans is a filamentous fungus and model organism for other Aspergillus species, such as A. flavus. A. flavus and some other Aspergillus species produce a toxin known as aflatoxin. This compound is a carcinogenic secondary metabolite produced by these organisms. A. nidulans is often used to study this pathway because it presents a conserved biosyntheticpathway that leads to the production of the related mycotoxin sterigmatocystin (ST). For my project, I have searched for chemicals that disrupt the activation of the biosynthetic pathway responsible for producing aflatoxin. Specifically, I screened for chemicals that inhibit the nuclear VeA-LaeA protein-protein interaction. This protein interaction has been previously shown to affect production of secondary metabolites, including aflatoxin, in Aspergillus species. The experiment was done by performing a yeast 2 hybrid strain, so that growth of the yeast is dependent upon the interaction of these two proteins. After performing the high throughput screening, I found one chemical of interest. However, application of this chemical on A. nidulans cultures did not prevent toxin production, fungal growth, or morphogenesis. It is possible that the compound is not incorporated in A. nidulans cells and reach the nucleus.