T-2 Toxin—The Most Toxic Trichothecene Mycotoxin: Metabolism, Toxicity, and Decontamination Strategies

Among trichothecenes, T-2 toxin is the most toxic fungal secondary metabolite produced by different Fusarium species. Moreover, T-2 is the most common cause of poisoning that results from the consumption of contaminated cereal-based food and feed reported among humans and animals. The food and feed most contaminated with T-2 toxin is made from wheat, barley, rye, oats, and maize. After exposition or ingestion, T-2 is immediately absorbed from the alimentary tract or through the respiratory mucosal membranes and transported to the liver as a primary organ responsible for toxin's metabolism. Depending on the age, way of exposure, and dosage, intoxication manifests by vomiting, feed refusal, stomach necrosis, and skin irritation, which is rarely observed in case of mycotoxins intoxication. In order to eliminate T-2 toxin, various decontamination techniques have been found to mitigate the concentration of T-2 toxin in agricultural commodities. However, it is believed that 100% degradation of this toxin could be not possible. In this review, T-2 toxin toxicity, metabolism, and decontamination strategies are presented and discussed.

Comparative Genomics and Transcriptomics Depict Marine Algicolous Arthrinium Species as Endosymbionts That Help Regulate Oxidative Stress in Brown Algae

The whole genome and transcriptome analyses were performed for prediction of the ecological characteristics of Arthrinium and the genes involved in gentisyl alcohol biosynthesis. Whole genome sequences of A. koreanum KUC21332 and A. saccharicola KUC21221 were analyzed, and the genes involved in interspecies interaction, carbohydrate-active enzymes, and secondary metabolites were investigated. Three of the seven genes associated with interspecies interactions shared by four Arthrinium spp. were involved in pathogenesis. A. koreanum and A. saccharicola exhibit the enzyme profiles similar to those observed in plant pathogens and endophytes rather than saprobes. Furthermore, six of the seven metabolites of known clusters identified in the genomes of the four Arthrinium spp. are associated with plant virulence. These results indicate that Arthrinium spp. are potentially pathogenic to plants. Subsequently, different conditions for gentisyl alcohol production in A. koreanum were established, and mRNA extracted from cultures of each condition was subjected to RNA-Seq to analyze the differentially-expressed genes. The gentisyl alcohol biosynthetic pathway and related biosynthetic gene clusters were identified, and gentisyl alcohol biosynthesis was significantly downregulated in the mannitol-supplemented group where remarkably low antioxidant activity was observed. These results indicate that gentisyl alcohol production in algicolous Arthrinium spp. is influenced by mannitol. It was suggested that the algicolous Arthrinium spp. form a symbiotic relationship that provides antioxidants when the photosynthetic activity of brown algae decreases in exchange for receiving mannitol. This is the first study to analyze the lifestyle of marine algicolous Arthrinium spp. at the molecular level and suggests a symbiotic mechanism with brown algae. It also improves the understanding of fungal secondary metabolite production via identification of the gentisyl alcohol biosynthetic gene clusters in Arthrinium spp.

Ecdysteroid kinase-like (EcKL) paralogs confer developmental tolerance to caffeine in Drosophila melanogaster

A unique aspect of metabolic detoxification in insects compared to other animals is the presence of xenobiotic phosphorylation, about which little is currently understood. Our previous work raised the hypothesis that members of the taxonomically restricted ecdysteroid kinase-like (EcKL) gene family encode the enzymes responsible for xenobiotic phosphorylation in the model insect Drosophila melanogaster (Diptera: Ephydroidea)—however, candidate detoxification genes identified in the EcKL family have yet to be functionally validated. Here, we test the hypothesis that EcKL genes in the rapidly evolving Dro5 clade are involved in the detoxification of plant and fungal toxins in D. melanogaster. The mining and reanalysis of existing data indicated multiple Dro5 genes are transcriptionally induced by the plant alkaloid caffeine and that adult caffeine susceptibility is associated with a novel naturally occurring indel in CG31370 (Dro5-8) in the Drosophila Genetic Reference Panel (DGRP). CRISPR-Cas9 mutagenesis of five Dro5 EcKLs substantially decreased developmental tolerance of caffeine, while individual overexpression of two of these genes—CG31300 (Dro5-1) and CG13659 (Dro5-7)—in detoxification-related tissues increased developmental tolerance. In addition, we found Dro5 loss-of-function animals also have decreased developmental tolerance of the fungal secondary metabolite kojic acid. Taken together, this work provides the first compelling functional evidence that EcKLs encode detoxification enzymes and suggests that EcKLs in the Dro5 clade are involved in the metabolism of multiple ecologically relevant toxins in D. melanogaster. We also propose a biochemical hypothesis for EcKL involvement in caffeine detoxification and highlight the many unknown aspects of caffeine metabolism in D. melanogaster and other insects.

Reconstitution of Polyketide-Derived Meroterpenoid Biosynthetic Pathway in Aspergillus oryzae

The heterologous gene expression system with Aspergillus oryzae as the host is an effective method to investigate fungal secondary metabolite biosynthetic pathways for reconstruction to produce un-natural molecules due to its high productivity and genetic tractability. In this review, we focus on biosynthetic studies of fungal polyketide-derived meroterpenoids, a group of bioactive natural products, by means of the A. oryzae heterologous expression system. The heterologous expression methods and the biosynthetic reactions are described in detail for future prospects to create un-natural molecules via biosynthetic re-design.

Bioinformatic insights on biochemical efficacy of a fungal metabolite: Asperyellone

The present study emphasizes the biochemical and bioinformatics insights of a fungal secondary metabolite identified as Asperyellone in detail. In brief, yellow color pigment, Asperyellone (AY) obtained from Aspergillus species...

Greensporone A, a Fungal Secondary Metabolite Suppressed Constitutively Activated AKT via ROS Generation and Induced Apoptosis in Leukemic Cell Lines

Greensporone A is a fungal secondary metabolite that has exhibited potential in vitro for anti-proliferative activity in vitro. We studied the anticancer activity of greensporone A in a panel of leukemic cell lines. Greensporone A-mediated inhibition of proliferation is found to be associated with the induction of apoptotic cell death. Greensporone A treatment of leukemic cells causes inactivation of constitutively activated AKT and its downstream targets, including members GSK3 and FOXO1, and causes downregulation of antiapoptotic genes such as Inhibitor of Apoptosis (IAPs) and Bcl-2. Furthermore, Bax, a proapoptotic member of the Bcl-2 family, was found to be upregulated in leukemic cell lines treated with greensporone A. Interestingly, gene silencing of AKT using AKT specific siRNA suppressed the expression of Bcl-2 with enhanced expression of Bax. Greensporone A-mediated increase in Bax/Bcl-2 ratio causes permeabilization of the mitochondrial membrane leading to the accumulation of cytochrome c in the cytoplasm. Greensporone A-induced cytochrome c accumulation causes the activation of caspase cascade and cleavage of its effector, poly(ADP-ribose) polymerase (PARP), leading to apoptosis. Greensporone A-mediated apoptosis in leukemic cells occurs through the generation of reactive oxygen species (ROS) due to depletion of glutathione (GSH) levels. Finally, greensporone A potentiated the anticancer activity of imatinib in leukemic cells. In summary, our study showed that greensporone A suppressed the growth of leukemic cells via induction of apoptotic cell death. The apoptotic cell death occurs by inhibition of AKT signaling and activation of the intrinsic apoptotic/caspase pathways. These results raise the possibility that greensporone A could be developed as a therapeutic agent for the treatment of leukemia and other hematological malignancies.