The Transcriptional Regulator Hbx1 Affects the Expression of Thousands of Genes in the Aflatoxin-Producing FungusAspergillus flavus

Abstract

In filamentous fungi, homeobox proteins are conserved transcriptional regulators described to control conidiogenesis and fruiting body formation. Eight homeobox (hbx) genes are found in the genome of the aflatoxin-producing ascomycete, Aspergillus flavus. While loss-of-function of seven of the eight genes had little to no effect on fungal growth and development, disruption of hbx1, resulted in aconidial colonies and lack of sclerotial production. Furthermore, the hbx1 mutant was unable to produce aflatoxins B1 and B2, cyclopiazonic acid and aflatrem. In the present study, hbx1 transcriptome analysis revealed that hbx1 has a broad effect on A. flavus gene expression, and the effect of hbx1 increases overtime, impacting more than five thousand protein-coding genes. Among the affected genes, those in the category of secondary metabolism (SM), followed by that of cellular transport, were the most affected. Specifically, regarding the effect of hbx1 on SM, we found that genes in 44 SM gene clusters where upregulated while 49 were downregulated in the absence of hbx1, including genes in the SM clusters responsible for the synthesis of asparasone, piperazine and aflavarin, all known to be associated with sclerotia. In addition, our study revealed that hbx1 affects the expression of other transcription factor genes involved in development, including the conidiation central regulatory pathway and flb genes.

Homeobox proteins are essential for fungal differentiation and secondary metabolism in Aspergillus nidulans

“…Moreover, the brlA mRNA level is also decreased in this mutant strain 46 . Deleting the hbxA homolog hbx1 shows similar results in A. flavus 44,45 . In other fungi, such as M. oryzae, Fusarium graminearum, and Ustilaginoidea virens, the putative hbxA orthologs (although similarity was low) are also involved in conidiogenesis.…”

“…In Saccharomyces cerevisiae, homeobox transcription factors are involved in filamentous growth, meiosis, and mating 37,42 . GRF10 has been shown to control the filamentous growth and pathogenicity of the human fungal pathogen Candida albicans in a mouse model 43 .Recently, the roles of fungal homeobox transcription factors have been characterized in two Aspergillus species, A. fumigatus and A. flavus [44][45][46] . In the aflatoxin-producing fungus A. flavus, eight genes coding for homeobox-type proteins have been characterized.…”

“…Recently, the roles of fungal homeobox transcription factors have been characterized in two Aspergillus species, A. fumigatus and A. flavus [44][45][46] . In the aflatoxin-producing fungus A. flavus, eight genes coding for homeobox-type proteins have been characterized.…”

Impact of the Cultivation Technique on the Production of Secondary Metabolites by Chrysosporium lobatum TM-237-S5, Isolated from the Sponge Acanthella cavernosa

“…A 2019 collaborative review highlighted the present state of knowledge and raised a multitude of open questions regarding the diversity and function of fungi in marine ecosystems [13].The symbiont assemblages inside the sponge are well organized in biofilms or dense colonies and are stabilized in the skeleton network over time [14,15]. This certainly impacts their development steps and the expression of biosynthetic clusters of secondary metabolites because it is now well documented that, in fungi, secondary metabolism and life cycle among fungi are co-regulated at the genomic level [16][17][18].This idea drives us to compare the metabolic profile of fungi cultivated on a gar slants and in liquid state. The result is that solid-state cultivation often leads to larger molecular diversity than classical liquid state fermentation LSF [19][20][21].…”

“…The symbiont assemblages inside the sponge are well organized in biofilms or dense colonies and are stabilized in the skeleton network over time [14,15]. This certainly impacts their development steps and the expression of biosynthetic clusters of secondary metabolites because it is now well documented that, in fungi, secondary metabolism and life cycle among fungi are co-regulated at the genomic level [16][17][18].…”