ZfpA-Dependent Quorum Sensing Shifts in Morphology and Secondary Metabolism in Aspergillus flavus

Abstract

Development of the fungal pathogen Aspergillus flavus involves the balance of asexual spores (conidia) and overwintering hardened hyphal masses (sclerotia). This balance is achieved by an oxylipin-based density-dependent mechanism regulating the switch from sclerotia to conidia as population density increases in A. flavus. Here, we show the transcription factor ZfpA, required for normal oxylipin synthesis, regulates the morphology switch. ZfpA overexpression (OE::zfpA) accelerates the shift leading to increased conidial production and reduced sclerotial production under conditions normally supporting sclerotia formation. In contrast, zfpA deletion (ΔzfpA) produces more sclerotia than wild-type control. These morphology changes are coupled with changes in tissue-specific secondary metabolites. Specifically, the production of four sclerotial metabolites (oxyasparasone A, hydroxyaflatrem, aflavinine, and kotanin) decreases in OE::zfpA whereas the hyphal metabolite aspergillic acid is upregulated in this mutant. Chemical profiling of OE::zfpA compared to a double mutant where the aspergillic acid non-ribosomal synthetase was deleted in the OE::zfpA background confirmed synthesis of known aspergillic acid pathway products as well as putative Val-derived pyrazinones involved in metal chelation. These findings offer valuable insights into the quorum sensing networks connecting fungal development and tissue-specific secondary metabolite production.