Insight into the global regulation of laeA in Aspergillus flavus based on proteomic profiling

In Aspergillus flavus, laeA affects cell morphology and contributes to the production of secondary metabolites (SMs) production including aflatoxin, cyclopiazonic acid, and aflatrem. Here, we investigated the function of this transcription factor by performing proteomics analysis of the wild-type (WT) and ΔlaeA mutant growing on corn. Notably, our proteomics profile confirmed the functions of extracellular hydrolases, conidial hydrophobin, and response to oxidative stress during the induction of aflatoxin biosynthesis regulated by laeA. Unexpectedly, deletion of laeA resulted in the significant upregulation of the NAD⁺-dependent histone deacetylase sirA involved in silencing SM clusters via chromatin remodeling. Accompanying the chromatin modification, enzymes participating in SM, including aflatoxin and cyclopiazonic acid biosynthesis, were drastically decreased. Another unexpected finding was that enzymes in the recently identified ustiloxin B biosynthesis pathway might be regulated by laeA. These data provided novel insights into the complex regulation of laeA and suggested a potential link between laeA deletion, NAD⁺-dependent histone deacetylation, and SM production in A. flavus.