TL;DR: The 12,13-epoxytrichothecenes, a group of sesquiterpenoid fungal antibiotics, inhibit protein synthesis in eukaryotic cells but do not share a common mode of action as discussed by the authors.
Abstract: The 12,13-epoxytrichothecenes, a group of sesquiterpenoid fungal antibiotics, inhibit protein synthesis in eukaryotic cells but do not share a common mode of action. Trichodermin stabilizes polyribosomes, prevents their disaggregation by puromycin, and also prevents the release of nascent peptides from ribosomes by puromycin. Nivalenol, T-2 toxin, and verrucarin A cause rapid and almost quantitative breakdown of polyribosomes in H-HeLa cells, a process which is inhibited by anisomycin, cycloheximide, or trichodermin. Similar effects of trichodermin, nivalenol, and verrucarin A are also observed in yeast spheroplasts. We conclude that nivalenol, T-2 toxin, and verrucarin A are potent and highly selective inhibitors of polypeptide chain initiation in eukaryotes, whereas trichodermin inhibits chain elongation and (or) termination. We have compared the structural formulae of various trichothecenes and suggest that the presence of substituents on carbon-15 of the common trichothecene ring may be important in determining the precise modes of action of this group of compounds.
TL;DR: Results suggest that the gene for trichodermin resistance in yeast specifies ribosomal protein L3, which is similar to that exhibited by strains carrying a chromosome copy of tcm1.
Abstract: Yeast cells sensitive to the eukaryotic protein synthesis inhibitor trichodermin have been transformed with autonomously replicating recombinant plasmids carrying DNA fragments of the genome of a trichodermin-resistant yeast strain. After selection for trichodermin-resistant cells, several transformants yielded a plasmid containing a 13.5-kilobase (kb) DNA fragment that encodes the trichodermin resistance gene, tcm1, and the gene for ribosomal protein L3, the largest of the yeast ribosomal proteins. Cells carrying this plasmid are resistant to trichodermin and to the related drug verrucarin A as well as to the unrelated drug anisomycin. This pattern of resistance is similar to that exhibited by strains carrying a chromosomal copy of tcm1. Moreover, polyribosomes prepared from transformed cells are resistant to trichodermin when tested in an in vitro protein synthesis assay. Subcloning of the 13.5-kb DNA fragment revealed that the gene for tcm1 and the gene for protein L3 are contained within a 3.2-kb segment. These results suggest that the gene for trichodermin resistance in yeast specifies ribosomal protein L3.
TL;DR: The results point to the significant role of tri5 in the production of trichodermin and in the antifungal activity of T. brevicompactum, a simple trichothecene-type toxin that shares the first steps of the sesquiterpene biosynthetic pathway with other phytotoxic trichoescenes from Fusarium spp.
TL;DR: Results indicated that harzianum A was synthesized directly by esterification of trichodermol with octa-2Z,4E,6E-trienedioic acid in the harZianum-A-producing strains, and trichodermin and/or harzia produced trichothecenes on all media investigated.
Abstract: Trichoderma brevicompactum, T viride, T harzianum, T atroviride, T longibrachiatum, T erinaceum, T citrinoviride, and Hypocrea lutea were screened for production of trichothecenes after growth on one or several solid and liquid media Trichothecenes were detected by liquid chromatography combined with online UV/vis spectroscopy and electrospray high-resolution mass spectrometry T brevicompactum produced trichodermin and/or harzianum A on all media investigated, with liquid media yielding the largest amounts Detection of octa-2Z,4E,6E-trienedioic acid in the harzianum-A-producing strains indicated that harzianum A was synthesized directly by esterification of trichodermol with octa-2Z,4E,6E-trienedioic acid Both the T viride strain from which trichodermin was originally isolated and the T harzianum strain from which harzianum A was originally isolated were shown to belong to T brevicompactum based on four independent criteria: metabolite profiles, micromorphology, macromorphology on yeast extract sucrose agar and potato dextrose agar, and DNA sequences of the ITS1/ITS2 regions of the nuclear ribosomal DNA