Publications by authors named "Slavica Janevska"

produces the mycotoxin fumonisin B (FB), which disrupts sphingolipid biosynthesis by inhibiting ceramide synthase and affects the health of plants, animals, and humans. The means by which protects itself from its own mycotoxin are not completely understood. Some fumonisin () cluster genes do not contribute to the biosynthesis of the compound, but their function has remained enigmatic.

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The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental disorders such as therapy-refractory depression, alcohol use disorder and anorexia nervosa. Psilocybin has been designated a 'Breakthrough Therapy' by the US Food and Drug Administration, and therefore a sustainable production process must be established to meet future market demands. Here, we present the development of an in vivo psilocybin production chassis based on repression of l-tryptophan catabolism.

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Background: Fusarium fujikuroi is a pathogen of rice causing diverse disease symptoms such as 'bakanae' or stunting, most likely due to the production of various natural products (NPs) during infection. Fusaria have the genetic potential to synthesize a plethora of these compounds with often diverse bioactivity. The capability to synthesize NPs exceeds the number of those being produced by far, implying a gene regulatory network decisive to induce production.

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Sphingofungins are sphinganine analog mycotoxins acting as inhibitors of serine palmitoyl transferases, enzymes responsible for the first step in the sphingolipid biosynthesis. Eukaryotic cells are highly organized with various structures and organelles to facilitate cellular processes and chemical reactions, including the ones occurring as part of the secondary metabolism. We studied how sphingofungin biosynthesis is compartmentalized in the human-pathogenic fungus , and we observed that it takes place in the endoplasmic reticulum (ER), ER-derived vesicles, and the cytosol.

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It has been discovered that plant pathogens produce effectors that spread via plasmodesmata (PD) to allow modulation of host processes in distal uninfected cells. f. sp.

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Sphingofungins belong to a group of structurally related sphingolipid inhibitors produced by fungi, which specifically inhibit serine palmitoyl transferases, enzymes catalyzing the initial step during sphingolipid biosynthesis. Sphingolipids are integral parts of the eukaryotic cell membrane, and disturbances in their homeostasis have been linked to various human diseases. It has been suggested that external interventions, sphingolipid inhibitors, may represent a promising approach for alternative therapies.

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Fumonisin (FB) mycotoxins produced by species of the genus detrimentally affect human and animal health upon consumption, due to the inhibition of ceramide synthase. In the present work, we set out to identify mechanisms of self-protection employed by the FB producer FB biosynthesis was shown to be compartmentalized, and two cluster-encoded self-protection mechanisms were identified. First, the ATP-binding cassette transporter Fum19 acts as a repressor of the gene cluster.

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Dimethylallyltryptophan synthases catalyze the regiospecific transfer of (oligo)prenylpyrophosphates to aromatic substrates like tryptophan derivatives. These reactions are key steps in many biosynthetic pathways of fungal and bacterial secondary metabolites. investigations on recombinant DMATS1 from identified the enzyme as the first selective reverse tryptophan--1 prenyltransferase of fungal origin.

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The pathogenic fungus is able to adapt to extremely variable environmental conditions. The genome contains four genes coding for mitogen-activated protein kinases (MAPKs), which are important regulatory knots involved in diverse cellular responses. From a clinical perspective, MAPK activity has been connected to salvage pathways, which can determine the failure of effective treatment of invasive mycoses using antifungal drugs.

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Here we present the identification and characterization of the H3K4-specific histone methyltransferase Set1 and its counterpart, the Jumonji C demethylase Kdm5, in the rice pathogen Fusarium fujikuroi. While Set1 is responsible for all detectable H3K4me2/me3 in this fungus, Kdm5 antagonizes the H3K4me3 mark. Notably, deletion of both SET1 and KDM5 mainly resulted in the upregulation of genome-wide transcription, also affecting a large set of secondary metabolite (SM) key genes.

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The fungus Fusarium fujikuroi causes bakanae disease of rice due to its ability to produce the plant hormones, the gibberellins. The fungus is also known for producing harmful mycotoxins (e.g.

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In this work, we present a comprehensive analysis of the H3K36 histone methyltransferases Set2 and Ash1 in the filamentous ascomycete In , one single methyltransferase, Set2, confers all H3K36 methylation, while there are two members of the Set2 family in filamentous fungi, and even more H3K36 methyltransferases in higher eukaryotes. Whereas the yeast Set2 homolog has been analyzed in fungi previously, the second member of the Set2 family, designated Ash1, has not been described for any filamentous fungus. Western blot and ChIP-Seq analyses confirmed that Set2 and Ash1 are H3K36-specific histone methyltransferases that deposit H3K36me3 at specific loci: Set2 is most likely responsible for H3K36 methylation of euchromatic regions of the genome, while Ash1 methylates H3K36 at the subtelomeric regions (facultative heterochromatin) of all chromosomes, including the accessory chromosome XII.

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The fungus Fusarium fujikuroi causes "bakanae" disease of rice due to its ability to produce gibberellins (GAs), a family of plant hormones. Recent genome sequencing revealed the genetic capacity for the biosynthesis of 46 additional secondary metabolites besides the industrially produced GAs. Among them are the pigments bikaverin and fusarubins, as well as mycotoxins, such as fumonisins, fusarin C, beauvericin, and fusaric acid.

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Fusarium fujikuroi causes bakanae ("foolish seedling") disease of rice which is characterized by hyper-elongation of seedlings resulting from production of gibberellic acids (GAs) by the fungus. This plant pathogen is also known for production of harmful mycotoxins, such as fusarins, fusaric acid, apicidin F and beauvericin. Recently, we generated the first de novo genome sequence of F.

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The PKS-NRPS-derived tetramic acid equisetin and its -desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., .

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The range of secondary metabolites (SMs) produced by the rice pathogen Fusarium fujikuroi is quite broad. Several polyketides, nonribosomal peptides and terpenes have been identified. However, no products of dimethylallyltryptophan synthases (DMATSs) have been elucidated, although two putative DMATS genes are present in the F.

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In the two fungal pathogens and , secondary metabolites (SMs) are fitness and virulence factors and there is compelling evidence that the coordination of SM gene expression is under epigenetic control. Here, we characterized Ccl1, a subunit of the COMPASS complex responsible for methylating lysine 4 of histone H3 (H3K4me). We show that Ccl1 is not essential for viability but a regulator of genome-wide trimethylation of H3K4 (H3K4me3).

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The 2H-pyran-2-one gibepyrone A and its oxidized derivatives gibepyrones B-F have been isolated from the rice pathogenic fungus Fusarium fujikuroi already more than 20 years ago. However, these products have not been linked to the respective biosynthetic genes, and therefore, their biosynthesis has not yet been analyzed on a molecular level. Feeding experiments with isotopically labeled precursors clearly supported a polyketide origin for the formal monoterpenoid gibepyrone A, whereas the terpenoid pathway could be excluded.

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Fusaric acid (FSA) is a mycotoxin produced by several fusaria, including the rice pathogen Fusarium fujikuroi. Genes involved in FSA biosynthesis were previously identified as a cluster containing a polyketide synthase (PKS)-encoding (FUB1) and four additional genes (FUB2-FUB5). However, the biosynthetic steps leading to FSA as well as the origin of the nitrogen atom, which is incorporated into the polyketide backbone, remained unknown.

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The plant pathogenic fungus Fusarium fujikuroi is the causal agent of bakanae disease on rice due to its ability to produce gibberellins. Besides these phytohormones, F. fujikuroi is able to produce several other secondary metabolites (SMs).

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The fungus F. fujikuroi is well known for its production of gibberellins causing the 'bakanae' disease of rice. Besides these plant hormones, it is able to produce other secondary metabolites (SMs), such as pigments and mycotoxins.

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