Harzianums A and B produced by a fungal strain, <i>Hypocrea</i> sp. F000527, and their cytotoxicity against tumor cell lines

Jin, Hui; Lee, J H; Zhang, Wei‐Dong; Lee, H B; Hong, Young-Shick; Kim, Y H; Lee, Jun Young

doi:10.1080/10286020500531977

Cited by 16 publications

(20 citation statements)

References 5 publications

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“…Lee et al (2005) reported production of harzianum A by a strain (F000527 = CBS 113214) isolated directly from a soil sample collected in Daejeon, Korea, and identified by DNA sequences as a Hypocrea sp. Recently, a new trichothecene homologue, harzianum B, was isolated from the same strain (Jin et al 2007). We received this strain too late to include in our phylogenetic analysis, but we have identified it also as T. arundinaceum.…”

Section: Discussionmentioning

confidence: 97%

The Trichoderma brevicompactum clade: a separate lineage with new species, new peptaibiotics, and mycotoxins

et al. 2008

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The Brevicompactum clade is recognized as a separate lineage in Trichoderma/Hypocrea. This includes T. brevicompactum and the new species T. arundinaceum, T. turrialbense, T. protrudens and Hypocrea rodmanii. The closest relative of the Brevicompactum clade is the Lutea clade. With the exception of H. rodmanii, all members of this clade produce the simple trichothecene-type toxins harzianum A or trichodermin. All members of the clade produce peptaibiotics, including alamethicins. Strains previously reported as T. harzianum (ATCC 90237), T. viride (NRRL 3199) or Hypocrea sp. (F000527, CBS 113214) to produce trichothecenes are reidentified as T. arundinaceum. The Brevicompactum clade is not closely related to species that have biological application.

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Section: Discussionmentioning

confidence: 97%

The Trichoderma brevicompactum clade: a separate lineage with new species, new peptaibiotics, and mycotoxins

et al. 2008

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“…Finally, the solid obtained was resuspended in acetonitrile and stored at Ϫ30°C. HA was identified by nuclear magnetic resonance (NMR) (27) and quantified by using a standard curve.…”

Section: Methodsmentioning

confidence: 99%

Identification of Loci and Functional Characterization of Trichothecene Biosynthesis Genes in Filamentous Fungi of the Genus Trichoderma

Cardoza

Malmierca

Hermosa

et al. 2011

Appl Environ Microbiol

129

196

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Trichothecenes are mycotoxins produced by Trichoderma, Fusarium, and at least four other genera in the fungal order Hypocreales. Fusarium has a trichothecene biosynthetic gene (TRI) cluster that encodes transport and regulatory proteins as well as most enzymes required for the formation of the mycotoxins. However, little is known about trichothecene biosynthesis in the other genera. Here, we identify and characterize TRI gene orthologues (tri) in Trichoderma arundinaceum and Trichoderma brevicompactum. Our results indicate that both Trichoderma species have a tri cluster that consists of orthologues of seven genes present in the Fusarium TRI cluster. Organization of genes in the cluster is the same in the two Trichoderma species but differs from the organization in Fusarium. Sequence and functional analysis revealed that the gene (tri5) responsible for the first committed step in trichothecene biosynthesis is located outside the cluster in both Trichoderma species rather than inside the cluster as it is in Fusarium. Heterologous expression analysis revealed that two T. arundinaceum cluster genes (tri4 and tri11) differ in function from their Fusarium orthologues. The Tatri4-encoded enzyme catalyzes only three of the four oxygenation reactions catalyzed by the orthologous enzyme in Fusarium. The Tatri11-encoded enzyme catalyzes a completely different reaction (trichothecene C-4 hydroxylation) than the Fusarium orthologue (trichothecene C-15 hydroxylation). The results of this study indicate that although some characteristics of the tri/TRI cluster have been conserved during evolution of Trichoderma and Fusarium, the cluster has undergone marked changes, including gene loss and/or gain, gene rearrangement, and divergence of gene function.Trichothecenes are a group of over 200 sesquiterpenoidderived secondary metabolites that vary by the pattern of oxygenations and esterifications of a core tricyclic structure with an epoxide function. These metabolites are produced by species in at least six genera of the fungal order Hypocreales (class Sordariomycetes): Fusarium, Myrothecium, Spicellum, Stachybotrys, Trichoderma, and Trichothecium. Trichothecenes are considered mycotoxins because they are often found as contaminants in food and animal feed and they can induce vomiting, alimentary hemorrhaging, and dermatitis in humans and livestock. These symptoms most likely result from the ability of trichothecenes to inhibit protein synthesis (40) and/or to induce apoptosis in eukaryotic cells (45). Trichothecenes also can act as immunosuppressors (51) and neurotoxins (36). Trichothecenes are phytotoxic (17). Previously (56), we observed that overproduction of trichodermin in Trichoderma brevicompactum reduced tomato seed germination and plant growth while increasing the size of the lesions produced when the pathogen was artificially inoculated on tomato plants previously colonized by Trichoderma spp.

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“…cDNAs were synthesized by using 1 g of total RNA and a reverse transcription system based on the use of an oligo(dT) 15 primer (Promega, Madison, WI). cDNAs were quantified using a Nanodrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE).…”

Section: Methodsmentioning

confidence: 99%

“…HA and trichodermin have been studied widely in the last few decades (11)(12)(13)(14)(15)(16), and their biosynthetic pathways have been detailed almost completely (9). Research has expanded to examine the structure-function relationships of the various trichothecenes and their intermediates on plants and other fungi.…”

mentioning

confidence: 99%

Effects of Trichothecene Production on the Plant Defense Response and Fungal Physiology: Overexpression of the Trichoderma arundinaceum tri4 Gene in T. harzianum

Cardoza

McCormick

Malmierca

et al. 2015

Appl Environ Microbiol

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dTrichothecenes are fungal sesquiterpenoid compounds, the majority of which have phytotoxic activity. They contaminate food and feed stocks, resulting in potential harm to animals and human beings. Trichoderma brevicompactum and T. arundinaceum produce trichodermin and harzianum A (HA), respectively, two trichothecenes that show different bioactive properties. Both compounds have remarkable antibiotic and cytotoxic activities, but in addition, trichodermin is highly phytotoxic, while HA lacks this activity when analyzed in vivo. Analysis of Fusarium trichothecene intermediates led to the conclusion that most of them, with the exception of the hydrocarbon precursor trichodiene (TD), have a detectable phytotoxic activity which is not directly related to the structural complexity of the intermediate. In the present work, the HA intermediate 12,13-epoxytrichothec-9-ene (EPT) was produced by expression of the T. arundinaceum tri4 gene in a transgenic T. harzianum strain that already produces TD after transformation with the T. arundinaceum tri5 gene. Purified EPT did not show antifungal or phytotoxic activity, while purified HA showed both antifungal and phytotoxic activities. However, the use of the transgenic T. harzianum tri4 strain induced a downregulation of defense-related genes in tomato plants and also downregulated plant genes involved in fungal root colonization. The production of EPT by the transgenic tri4 strain raised levels of erg1 expression and reduced squalene accumulation while not affecting levels of ergosterol. Together, these results indicate the complex interactions among trichothecene intermediates, fungal antagonists, and host plants.A number of Trichoderma species are known for the ability to act as important biocontrol agents against phytopathogenic fungi (1, 2). Trichoderma species are able to act as biofertilizers, to induce plant defense responses, and to increase tolerance to abiotic stresses (3, 4). Trichoderma arundinaceum and T. brevicompactum also produce trichothecenes, sesquiterpenoid compounds which are harmful to plants and to the animals which consume contaminated food or feed stocks. Several studies on the structure-activity relationships of Fusarium trichothecene toxins in alga, plant, and animal models (5-7) indicate that certain Fusarium trichothecenes and intermediates have different toxic effects. Using an Arabidopsis leaf assay, Desjardins and coworkers found that toxicity varied Ͼ200-fold between different trichothecene compounds, while trichodiene (TD), a hydrocarbon precursor, was not phytotoxic (6).Biosynthesis of trichothecenes starts with the cyclization of farnesyl diphosphate (FPP), catalyzed by the terpene cyclase trichodiene synthase encoded by tri5 (8), to produce TD. In Trichoderma, TD is then oxygenated at C-2, C-11, and C-13 by a P450 monooxygenase encoded by tri4 (9, 10) to give the intermediate isotrichodiol, which is nonenzymatically converted to 12,13-epoxytrichothec-9-ene (EPT). The oxygenation of these three carbons is a characteristic that Trichoderma...

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Harzianums A and B produced by a fungal strain, Hypocrea sp. F000527, and their cytotoxicity against tumor cell lines

Cited by 16 publications

References 5 publications

The Trichoderma brevicompactum clade: a separate lineage with new species, new peptaibiotics, and mycotoxins

The Trichoderma brevicompactum clade: a separate lineage with new species, new peptaibiotics, and mycotoxins

Identification of Loci and Functional Characterization of Trichothecene Biosynthesis Genes in Filamentous Fungi of the Genus Trichoderma

Effects of Trichothecene Production on the Plant Defense Response and Fungal Physiology: Overexpression of the Trichoderma arundinaceum tri4 Gene in T. harzianum

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