Abstract
The genus Aspergillus includes important plant pathogens, opportunistic human pathogens and mycotoxigenic fungi. In these organisms, secondary metabolism and morphogenesis are subject to a complex genetic regulation. Here we functionally characterized urdA, a gene encoding a putative helix-loop-helix (HLH)-type regulator in the model fungus Aspergillus nidulans. urdA governs asexual and sexual development in strains with a wild-type veA background; absence of urdA resulted in severe morphological alterations, with a significant reduction of conidial production and an increase in cleistothecial formation, even in the presence of light, a repressor of sex. The positive effect of urdA on conidiation is mediated by the central developmental pathway (CDP). However, brlA overexpression was not sufficient to restore wild-type conidiation in the ΔurdA strain. Heterologous complementation of ΔurdA with the putative Aspergillus flavus urdA homolog also failed to rescue conidiation wild-type levels, indicating that both genes perform different functions, probably reflected by key sequence divergence. UrdA also represses sterigmatocystin (ST) toxin production in the presence of light by affecting the expression of aflR, the activator of the ST gene cluster. Furthermore, UrdA regulates the production of several unknown secondary metabolites, revealing a broader regulatory scope. Interestingly, UrdA affects the abundance and distribution of the VeA protein in hyphae, and our genetics studies indicated that veA appears epistatic to urdA regarding ST production. However, the distinct fluffy phenotype of the ΔurdAΔveA double mutant suggests that both regulators conduct independent developmental roles. Overall, these results suggest that UrdA plays a pivotal role in the coordination of development and secondary metabolism in A. nidulans.
Highlights
Numerous fungal species synthesize a variety of natural products, called secondary metabolites, which are not necessary for the organism to survive but can confer an ecological advantage [1,2,3]
Aspergillus nidulans, a filamentous fungus that has been used as a model organism for more than 60 years [6], is capable of producing a mycotoxin known as sterigmatocystin (ST)
The phylogenetic tree shows that orthologs from species of the genera Penicillium, Rasamsonia, Byssochlamys and Talaromyces clustered in one clade, while orthologs from Aspergillus species clustered in four additional clades, with those from A. calidostus, A. nidulans, A. ochraceoroseus, A. rambelli, A. sydowii and A. versicolor being the most divergent ones (Figure S2)
Summary
Numerous fungal species synthesize a variety of natural products, called secondary metabolites, which are not necessary for the organism to survive but can confer an ecological advantage [1,2,3]. Many fungal secondary metabolites produced are bioactive and have beneficial properties, whereas others are detrimental to plants, animals and human health. Aspergillus nidulans, a filamentous fungus that has been used as a model organism for more than 60 years [6], is capable of producing a mycotoxin known as sterigmatocystin (ST). Sterigmatocystin is similar to a highly carcinogenic compound known as aflatoxins (AF) [7,8,9,10]
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