Aspergillus flavus secondary metabolism: one species, many compounds

Aspergillus flavus produces toxic and carcinogenic aflatoxins. In silico analysis of the A. flavus genome revealed 56 gene clusters encoding for secondary metabolites (SMs). Although about 20 SMs have been identified from A. flavus cultures, studies by our group and others have experimentally assigned metabolites to just ten A. flavus gene clusters. We are interested in how these SMs affect fungal development, survival, virulence, and their ability to potentiate aflatoxin toxicity. Recent studies on uncharacterized SM gene clusters have revealed the following metabolites: (1) Asparasone (cluster 27) is a polyketide-derived pigment found in sclerotia that imparts UV and heat resistance to sclerotia and exhibits antiinsectan/antifeedant properties. (2) Another polyketide-derived sclerotial metabolite, aflavarin (cluster 39), demonstrates antiinsectan properties and was also shown to play a role in sclerotial production.  Analysis of RNA-Seq data from a number of A. flavus strains growing on artificial media indicates that approximately half of the SM gene clusters are silent or expressed at very low levels. Overexpression of the pathway-specific transcriptional activator in cluster 23, coupled with comparative metabolomics enabled identification of (3) a family of hybrid PKS-NRPS-derived 2-pyridones, designated leporins, never before described in A. flavus involved in development and possibly in iron homeostasis. Our preliminary results indicate that cluster 11 encodes for aspergillic acid (4), a hydroxamic acid-containing mycotoxin that also possesses antibacterial properties. The metabolites that play a role in fungal development, virulence or pathogenicity could serve as targets for disease control and reduction of aflatoxin contamination by A. flavus.