The aim of this systematic review is to provide an update on the occurrence and co-occurrence of selected non-regulated mycotoxins and provide an overview of current regulations. Fifteen non-regulated mycotoxins were found in 19 food categories worldwide. On top of that, 38 different combinations of non-regulated mycotoxins were found, with mixtures varying from binary combinations up to 12 mycotoxins. Taking into consideration the amount of evidence regarding the prevalence and co-occurrence of non-regulated mycotoxins, future steps should be taken considering continuous monitoring, scientific exchange, and generation of high-quality data. To enhance data quality, guidelines outlining the minimum quality criteria for both occurrence data and metadata are needed. By doing so, we can effectively address concerns related to the toxicity of non-regulated mycotoxins. Furthermore, obtaining more data concerning the co-occurrence of both regulated and non-regulated mycotoxins could aid in supporting multiple chemical risk assessment methodologies. Implementing these steps could bolster food safety measures, promote evidence-based regulations, and ultimately safeguard public health from the potential adverse effects of non-regulated mycotoxins.

Chromatin structure is a major regulator of DNA-associated processes, such as transcription, DNA repair, and replication. Histone post-translational modifications, or PTMs, play a key role on chromatin dynamics. PTMs are involved in a wide range of biological processes in eukaryotes, including fungal species. Their deposition/removal and their underlying functions have been extensively investigated in yeasts but much less in other fungi. Nonetheless, the major role of histone PTMs in regulating primary and secondary metabolisms of filamentous fungi, including human and plant pathogens, has been pinpointed. In this review, an overview of major identified PTMs and their respective functions in fungi is provided, with a focus on filamentous fungi when knowledge is available. To date, most of these studies investigated histone acetylations and methylations, but the development of new methodologies and technologies increasingly allows the wider exploration of other PTMs, such as phosphorylation, ubiquitylation, sumoylation, and acylation. Considering the increasing number of known PTMs and the full range of their possible interactions, investigations of the subsequent Histone Code, i.e., the biological consequence of the combinatorial language of all histone PTMs, from a functional point of view, are exponentially complex. Better knowledge about histone PTMs would make it possible to efficiently fight plant or human contamination, avoid the production of toxic secondary metabolites, or optimize the industrial biosynthesis of certain beneficial compounds.

Chromatin is a highly dynamic structure that closely relates with gene expression in eukaryotes. ATP-dependent chromatin remodelling, histone post-translational modification and DNA methylation are the main ways that mediate such plasticity. The histone variant H2A.Z is frequently encountered in eukaryotes, and can be deposited or removed from nucleosomes by chromatin remodelling complex SWR1 or INO80, respectively, leading to altered chromatin state. H2A.Z has been found to be involved in a diverse range of biological processes, including genome stability, DNA repair and transcriptional regulation. Due to their formidable production of secondary metabolites, filamentous fungi play outstanding roles in pharmaceutical production, food safety and agriculture. During the last few years, chromatin structural changes were proven to be a key factor associated with secondary metabolism in fungi. However, studies on the function of H2A.Z are scarce. Here, we summarize current knowledge of H2A.Z functions with a focus on filamentous fungi. We propose that H2A.Z is a potential target involved in the regulation of secondary metabolite biosynthesis by fungi.

Fusarium head blight is a destructive disease of grains resulting in reduced yields and contamination of grains with mycotoxins worldwide; Fusarium graminearum is its major causal agent. Chromatin structure changes play key roles in regulating mycotoxin biosynthesis in filamentous fungi. Using a split-marker approach in three F. graminearum strains INRA156, INRA349 and INRA812 (PH-1), we knocked out the gene encoding H2A.Z, a ubiquitous histone variant reported to be involved in a diverse range of biological processes in yeast, plants and animals, but rarely studied in filamentous fungi. All ΔH2A.Z mutants exhibit defects in development including radial growth, sporulation, germination and sexual reproduction, but with varying degrees of severity between them. Heterogeneity of osmotic and oxidative stress response as well as mycotoxin production was observed in ΔH2A.Z strains. Adding-back wild-type H2A.Z in INRA349ΔH2A.Z could not rescue the phenotypes. Whole genome sequencing revealed that, although H2A.Z has been removed from the genome and the deletion cassette is inserted at H2A.Z locus only, mutations occur at other loci in each mutant regardless of the genetic background. Genes affected by these mutations encode proteins involved in chromatin remodeling, such as the helicase Swr1p or an essential subunit of the histone deacetylase Rpd3S, and one protein of unknown function. These observations suggest that H2A.Z and the genes affected by such mutations are part or the same genetic interaction network. Our results underline the genetic plasticity of F. graminearum facing detrimental gene perturbation. These findings suggest that intergenic suppressions rescue deleterious phenotypes in ΔH2A.Z strains, and that H2A.Z may be essential in F. graminearum. This assumption is further supported by the fact that H2A.Z deletion failed in another Fusarium spp., i.e., the rice pathogen Fusarium fujikuroi. The function of histone variant H2A.Z has been widely studied in Saccharomyces cerevisiae and higher eukaryotes. However, there is a significant lack of knowledge of the role of H2A.Z and its regulation in filamentous fungi. Here we demonstrate for the first time that deleterious consequences of complete removal of H2A.Z from the genome of F. graminearum are mitigated by genetic suppression. The suppressors detected open new possibilities to investigate in more depth the network linking H2A.Z and other genes in F. graminearum and used to decipher unresolved questions concerning H2A.Z.

Consumption of cereals contaminated by mycotoxins poses health risks. For instance, Fumonisins B, mainly produced by Fusarium verticillioides and Fusariumproliferatum, and the type B trichothecene deoxynivalenol, typically produced by Fusarium graminearum, are highly prevalent on cereal grains that are staples of many cultural diets and known to represent a toxic risk hazard. In Peru, corn and other cereals are frequently consumed on a daily basis under various forms, the majority of food grains being sold through traditional markets for direct consumption. Here, we surveyed mycotoxin contents of market-bought grain samples in order to assess the threat these mycotoxins might represent to Peruvian population, with a focus on corn. We found that nearly one sample of Peruvian corn out of six was contaminated with very high levels of Fumonisins, levels mostly ascribed to the presence of F. verticillioides. Extensive profiling of Peruvian corn kernels for fungal contaminants could provide elements to refine the potential risk associated with Fusarium toxins and help define adapted food safety standards.

Climate change is driving a rise in the contamination of crops by mycotoxins, threatening global food security. If agrochemical use is to be reduced, environmentally friendly antimycotoxin solutions are urgently needed. This study aims to elucidate the antifungal and antimycotoxin modes of action of stilbenoid molecules from vine by-product extracts against Fusarium graminearum, the primary causal agent of Fusarium head blight in wheat and a main producer of type B trichothecene (TCTB) mycotoxins. E-resveratrol (RES), a monomer, and E-vitisin B (VIT), a tetramer, were selected as the targeted stilbenoids due to their predominance in vine extracts. VIT (8 µM) showed greater efficacy than RES (35 µM) in inhibiting spore germination, biomass production, and TCTB yield. To better understand their modes of action, a multi-omics approach combining mRNA-seq-based transcriptomics and LC-MS/MS-based untargeted metabolomics was employed. mRNA-seq data evidenced that VIT exposure altered the expression of nearly half of F. graminearum genes, whereas RES induced only minimal transcriptomic changes. Integrated with metabolomics data, our findings suggest that VIT's modes of action involves: (1) disruption of the fungal cell wall and plasma membrane via downregulation of sphingolipid metabolism, (2) inhibition of sporulation and hyphal growth, and (3) both direct and indirect interference with TCTB biosynthesis. These findings support the potential of viniculture waste-derived compounds as biofungicides, offering a dual benefit of reducing cereal mycotoxin contamination and valorising underused vine biomass.