Model Fungal Systems for Investigating Food Plant Mycotoxins

Abstract

Mycotoxins, e.g., aflatoxins , fumonisins, zearalenone, patulin, ochratoxins, etc., trigger serious health risks to human and animals. Mycotoxin contamination also interferes with the safe production of crops worldwide, resulting in significantly negative impact on world economy. Aflatoxins are carcinogenic mycotoxins produced mainly by aspergilli, such as Aspergillus flavus and A. parasiticus. Aflatoxins, when metabolically activated by hepatic cytochrome P450s (CYPs), trigger genotoxicity in mammals through the formation of reactive aflatoxin-8,9-exo-epoxide. The resulting 8,9-dihydro-8-(N ⁷-guanyl)-9-hydroxyaflatoxin adduct causes mutations (frameshift, GC to TA transversions) or DNA damage (chromosomal breaks, aberrations) and thus negatively affects human or animal health. The yeast Saccharomyces cerevisiae is a useful system for investigating the mechanisms of toxicity of aflatoxins, where mammalian CYPs can be functionally expressed to metabolically activate aflatoxins. Using recombinant S. cerevisiae, the consequences of CYP polymorphisms on the differential aflatoxin toxicity, effects of CYP-inhibitory phytochemicals on aflatoxin activation, transcriptional responses of cells to aflatoxins, etc., have been investigated. Of note, the aflatoxicosis could be ameliorated by S. cerevisiae cell walls. Aflatoxins interact with S. cerevisiae cell wall components, such as β-d-glucans, thus adsorbing/removing aflatoxins from the contaminated sources. Lastly, S. cerevisiae strains, such as gene deletion mutants, could also serve as useful genetic tools for identifying molecular targets or mode of actions of antifungal agents. This facilitates expedited development of new, safe antifungal drugs/fungicides, resulting in the effective control of aflatoxin-producing aspergilli.