Secondary chemicals protect mould from fungivory

Rohlfs, Marko; Albert, Martin; Keller, Nancy P.; Kempken, Frank

doi:10.1098/rsbl.2007.0338

Cited by 145 publications

(124 citation statements)

References 16 publications

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“…A. flavus, as well as other fungi, accumulates a variety of secondary metabolites in sclerotia (44,46,47). Some of these compounds protect the fungus against fungivorous predators (48). Our study revealed for the first time that the genes in cluster 39 are expressed mainly in sclerotia and are necessary for the formation of aflavarin.…”

Section: Figmentioning

confidence: 86%

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

et al. 2015

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eThe global regulatory veA gene governs development and secondary metabolism in numerous fungal species, including Aspergillus flavus. This is especially relevant since A. flavus infects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins are veA dependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of the A. flavus genome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show that veA is necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence of veA. One of the clusters under the influence of veA is cluster 39. The absence of veA results in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin.A spergillus flavus is a saprophytic filamentous fungus that is also able to colonize economically important crops such as peanuts, cotton, maize, and other oil seed crops during preharvest or storage. Its most efficient mode of dissemination is the production of airborne conidia. In addition, A. flavus produces resistant structures called sclerotia, which allow this fungus to survive adverse environmental conditions for long periods of time (1-3). This opportunistic pathogen produces a wide range of secondary metabolites, including aflatoxins (AFs). Among them, AFB1 is the most mutagenic and carcinogenic natural compound known (4-8). Ingestion of food products contaminated with AFs has been associated with hepatotoxicity, teratogenicity, immunosuppression, and liver cancer (6, 9). AF contamination also results in a negative impact on the economy in developed countries. In the United States alone A. flavus causes more than a billion dollar in losses per year due to contaminated crops (10). In addition to AFs, A. flavus is known to produce other mycotoxins, including cyclopiazonic acid (CPA), a suppressor of the calcium-dependent ATPase in the sarcoplasmic reticulum, and aflatrem, a tremogenic mycotoxin causative of neurological disorders (11,12).Studies of the A. flavus genome have revealed many gene clusters possibly connected to the synthesis of other secondary metabolites. Specifically, 55 different clusters were predicted based on the presence of genes encoding polyketide synthases (PKSs), non...

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Section: Figmentioning

confidence: 86%

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

et al. 2015

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“…However, deeper in the soil where light does not penetrate, VeA mediates an increase in af latoxin production. This in turn protects the colony and sclerotia from predation by worms and insects [building on recent studies by Rohlfs et al (23)] and hence helps A. parasiticus to survive in its ecological niche.…”

Section: Discussionmentioning

confidence: 99%

A key role for vesicles in fungal secondary metabolism

Chanda

Roze

Kang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

198

244

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Eukaryotes have evolved highly conserved vesicle transport machinery to deliver proteins to the vacuole. In this study we show that the filamentous fungus Aspergillus parasiticus employs this delivery system to perform new cellular functions, the synthesis, compartmentalization, and export of aflatoxin; this secondary metabolite is one of the most potent naturally occurring carcinogens known. Here we show that a highly pure vesicle-vacuole fraction isolated from A. parasiticus under aflatoxin-inducing conditions converts sterigmatocystin, a late intermediate in aflatoxin synthesis, to aflatoxin B 1 ; these organelles also compartmentalize aflatoxin. The role of vesicles in aflatoxin biosynthesis and export was confirmed by blocking vesicle-vacuole fusion using 2 independent approaches. Disruption of A. parasiticus vb1 (encodes a protein homolog of AvaA, a small GTPase known to regulate vesicle fusion in A. nidulans) or treatment with Sortin3 (blocks Vps16 function, one protein in the class C tethering complex) increased aflatoxin synthesis and export but did not affect aflatoxin gene expression, demonstrating that vesicles and not vacuoles are primarily involved in toxin synthesis and export. We also observed that development of aflatoxigenic vesicles (aflatoxisomes) is strongly enhanced under aflatoxin-inducing growth conditions. Coordination of aflatoxisome development with aflatoxin gene expression is at least in part mediated by Velvet (VeA), a global regulator of Aspergillus secondary metabolism. We propose a unique 2-branch model to illustrate the proposed role for VeA in regulation of aflatoxisome development and aflatoxin gene expression.S econdary metabolites, natural products generated by filamentous fungi, plants, bacteria, algae, and animals, have an enormous impact on humans due to their application in health, medicine, and agriculture. Many secondary metabolites are beneficial (antibiotics, statins, morphine, etc.), though phytotoxins (e.g., ricin, crotin, amygdalin) and fungal poisons called mycotoxins (e.g., aflatoxin, sterigmatocystin, fumonisin) are detrimental to humans and animals. To control or customize biosynthesis of these natural products we must understand how and where secondary metabolism is orchestrated within the cell.Vacuoles and vesicles are known to sequester secondary metabolites to protect host cells from self-toxicity (1). Enzymes involved in secondary metabolism are often found in vesicles and vacuoles, including those for biosynthesis of alkaloids (e.g., berberine, sanguinarine, camptotecin, and morphine; reviewed in refs. 1 and 2) and flavonoids (e.g., aurone) (reviewed in refs. 1 and 3) in plants and the nonribosomal peptide cyclosporin (4), the ␤-lactam antibiotic penicillin (5) (localization of ACVS is still controversial), and the polyketide aflatoxin (6-8) in fungi. However, the functional role of these compartments in secondary metabolism was unclear because these organelles potentially could be involved in synthesis, storage, protein turnover, transport, or export of...

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“…These microbial interactions activate SM clusters that produce bioactive compounds that offer protection for the organism, niche security, and a myriad of other benefits (27). One case in point is the Aspergillus fumigatus gliotoxin gene cluster.…”

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confidence: 99%

Cryptic Aspergillus nidulans Antimicrobials

Giles

Soukup

Lauer

et al. 2011

Appl Environ Microbiol

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Secondary metabolite (SM) production by fungi is hypothesized to provide some fitness attribute for the producing organisms. However, most SM clusters are "silent" when fungi are grown in traditional laboratory settings, and it is difficult to ascertain any function or activity of these SM cluster products. Recently, the creation of a chromatin remodeling mutant in Aspergillus nidulans induced activation of several cryptic SM gene clusters. Systematic testing of nine purified metabolites from this mutant identified an emodin derivate with efficacy against both human fungal pathogens (inhibiting both spore germination and hyphal growth) and several bacteria. The ability of catalase to diminish this antimicrobial activity implicates reactive oxygen species generation, specifically, the generation of hydrogen peroxide, as the mechanism of emodin hydroxyl activity.

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Secondary chemicals protect mould from fungivory

Cited by 145 publications

References 16 publications

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

Transcriptome Analysis of Aspergillus flavus Reveals veA -Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster

A key role for vesicles in fungal secondary metabolism

Cryptic Aspergillus nidulans Antimicrobials

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