Abstract
Aflatoxins are a potent carcinogenic mycotoxin and has become a research model of fungal secondary metabolism (SM). Via systematically investigating the APSES transcription factors (TFs), two APSES proteins were identified: AfRafA and AfStuA. These play central roles in the synthesis of mycotoxins including aflatoxin and cyclopiazonic acid, and fungal development and are consequently central to the pathogenicity of the aflatoxigenic A. flavus. Loss of AfRafA not only dramatically suppressed aflatoxin cluster expression, subsequently reducing toxin synthesis both in vitro and in vivo, but also impaired conidia and sclerotia development. More importantly, aflatoxin biosynthesis as well as conidia and sclerotia development were fully blocked in ΔAfStuA. In addition, our results supported that AfStuA regulated the aflatoxin synthesis in an AflR-dependent manner. Intriguingly, it was revealed that AfRafA and AfStuA exert an antagonistic role in the regulation of biosynthesis of cyclopiazonic acid. In summary, two global transcriptional regulators for fungal development, mycotoxin production, and seed pathogenicity of the A. flavus system have been established. The two novel regulators of mycotoxins are promising targets for future plant breeding and for the development of fungicides.
Highlights
IntroductionGenomic and metabolic investigations revealed that filamentous fungi host a large arsenal of secondary metabolites, many of which exhibited excellent bioactive activity and have been applied as therapeutic drugs (e.g., penicillium and lovastatin) in pharmaceutical development
Genomic and metabolic investigations revealed that filamentous fungi host a large arsenal of secondary metabolites, many of which exhibited excellent bioactive activity and have been applied as therapeutic drugs in pharmaceutical development
We systematically investigated all APSES TFs in the economically important pathogen A. flavus and our results showed that both AfRafA and AfStuA are essential for activating aflatoxin gene cluster expression and subsequent toxin synthesis, the development of conidia and sclerotia, as well as the colonization of plant seeds
Summary
Genomic and metabolic investigations revealed that filamentous fungi host a large arsenal of secondary metabolites, many of which exhibited excellent bioactive activity and have been applied as therapeutic drugs (e.g., penicillium and lovastatin) in pharmaceutical development. A number of secondary metabolites (SM) called mycotoxins (including aflatoxin, fumonisins, ochratoxin, trichothecenes, and cyclopiazonic acid) that widely exist on crops and agricultural products are severely threatening both human and animal health. Among these SM, Aflatoxin (AF) (and AFB1) was ranked as the most carcinogenic natural product that has been discovered (Squire, 1981; Lee and Adams, 1994). To eliminate negative effect by aflatoxins on human and animals, long-term and efficacious control strategies for both its synthesis and the producing fungi are urgently required To this end, it is significant to comprehensively and deeply understand the molecular mechanism for the regulation of aflatoxin production
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