Sesquiterpene Synthase from the Botrydial Biosynthetic Gene Cluster of the Phytopathogen <i>Botrytis cinerea</i>

Pinedo, Cristina; Wang, Chieh-Mei; Pradier, Jean‐Marc; Dalmais, Bérengère; Choquer, Mathias; Pêcheur, Pascal Le; Morgant, Georges; Collado, Isidro G.; Cane, David E.; Viaud, Muriel

doi:10.1021/cb800225v

Cited by 168 publications

(210 citation statements)

References 37 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…These include the abscisic acid and botrydial clusters in Botrytis cinerea (46,52), the Ao cluster in Aspergillus oryzae (42), and the gibberellin cluster in Fusarium fujikuroi (35). Of these clusters, only the B. cinerea abscisic acid cluster lacks a sesquiterpene cyclase gene that encodes the enzyme that catalyzes conversion of farnesyl pyrophosphate to the first committed intermediate in synthesis of the metabolite.…”

Section: Discussionmentioning

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

126

196

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

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

126

196

View full text Add to dashboard Cite

show abstract

“…In order to perform comparative gene expression studies by qPCR, oligonucleotides specific to the tomato plant defenserelated genes were used (33,34). These included PR1b1 and PR-P2 (salicylic acid [SA]-related genes) and PINI, PINII, and TomLoxA (jasmonic acid [JA]-related genes).…”

Section: Methodsmentioning

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

View full text Add to dashboard Cite

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...

show abstract

“…7 Recently, a genetically modified strain of B. cinerea, Dbcbot2, which is unable to produce botryanes but significantly overproduces botcinic acid (3) and its derivatives was constructed. 8 The higher production capacities of this strain prompted us to reinvestigate the metabolites produced by it. Additionally, in the course of our investigation on biotransformation with a wild strain of B. cinerea (UCA 992), a new metabolite with a botrylactone skeleton was isolated.…”

Section: Introductionmentioning

confidence: 99%

Botrylactone: new interest in an old molecule—review of its absolute configuration and related compounds

Moraga¹,

Pinedo²,

Durán-Patrón³

et al. 2011

Tetrahedron

Self Cite

View full text Add to dashboard Cite

a b s t r a c tThe absolute configuration of botrylactone, a unique compound with an interesting polyketide lactone skeleton with two oxirane bridges previously isolated from Botrytis cinerea and described as a powerful antibiotic, has been reviewed on the basis of sign of the optical rotation, NOE experiments and NMR method. The isolation of 7-deoxybotrylactone and 5-hydroxy-7-(4-hydroxydec-2(3)-enoyl) botrylactone enables us to characterize an intriguing new family of compounds with this interesting polyketide skeleton. A common biosynthetic origin with botcinin derivatives is proposed.

show abstract

Sesquiterpene Synthase from the Botrydial Biosynthetic Gene Cluster of the Phytopathogen Botrytis cinerea

Cited by 168 publications

References 37 publications

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

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

Botrylactone: new interest in an old molecule—review of its absolute configuration and related compounds

Contact Info

Product

Resources

About