Trichodiene is a precursor to trichothecenes

Zamir, Lolita O.; Gauthier, Maxime; Devor, Kenneth A.; Nadeau, Yves; Sauriol, Françoise

doi:10.1039/c39890000598

Cited by 28 publications

(17 citation statements)

References 2 publications

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“…In the pathway producing trichothecenes and related mycotoxins the first identified intermediate was trichodiene (TDN), which was proved to be originated from mevalonate via all-trans-FPP and nerodyl pyrophosphate, as reported in Figure 3 Zamir et al, 1989).…”

Section: Biosynthesismentioning

confidence: 99%

“…EFSA reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors In the pathway producing trichothecenes and related mycotoxins the first identified intermediate was trichodiene (TDN), which was proved to originate from mevalonate via alltrans-FPP and nerodyl pyrophosphate, as reported in Figure 3. Zamir et al, 1989).…”

Section: -467mentioning

confidence: 99%

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Scientific information on mycotoxins and natural plant toxicants

Battilani

Costa

Dossena

et al. 2009

EFSA Supporting Publications

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Section: Biosynthesismentioning

confidence: 99%

Section: -467mentioning

confidence: 99%

Scientific information on mycotoxins and natural plant toxicants

Battilani

Costa

Dossena

et al. 2009

EFSA Supporting Publications

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“…Three more compounds isolated from the feeding of 3a showed in the 13 C NMR spectra a large peak at C-16 ( Fig. 4): SOL, pre-SOL (a precursor to SOL (21)), and a dead end metabolite, 11␣-2␤,13␤-apotrichodiol, previously isolated from F. culmorum (14). This last metabolite was diacetylated after isolation to facilitate its purification (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…[15-2 H]12,13-Epoxytrichodiene (2c) was prepared from [15-2 H]trichodiene (14) by bromination of the deuterated trichodiene 14 to give the 9,10-dibromide, which was epoxidized, using m-chloroperoxybenzoic acid, to give the 12,13-epoxy-9,10-dibromide 15 (13). Compound 15 was debrominated using zinc dust in ethanol (20) to yield the desired deuterated epoxytrichodiene 2c.…”

Section: Resultsmentioning

confidence: 99%

“…The acetic anhydride and pyridine were evaporated under a stream of nitrogen, and the acetylated fraction was purified by analytical HPLC using 65% methanol, 35% water at 1 ml/min (t R ϭ 56 min). NMR characterization identified this compound as 11␣-2␤,13␤-apotrichodiol, which has previously been isolated from cultures of F. culmorum (14). …”

Section: Synthesis Of Compound 3a (Fig 2)-a Solution Of 2␣-acetoxy-1mentioning

confidence: 99%

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Biosynthesis of 3-Acetyldeoxynivalenol and Sambucinol

Zamir¹,

Nikolakakis²,

Huang³

et al. 1999

Journal of Biological Chemistry

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The first two oxygenation steps post-trichodiene in the biosyntheses of the trichothecenes 3-acetyldeoxynivalenol and sambucinol were investigated. The plausible intermediates 2-hydroxytrichodiene (2␣-and 2␤-) and 12,13-epoxytrichodiene and the dioxygenated compounds 12,13-epoxy-9,10-trichoene-2-ol (2␣-and 2␤-) were prepared specifically labeled with stable isotopes. They were then fed separately and/or together to Fusarium culmorum cultures, and the derived trichothecenes were isolated, purified, and analyzed. The stable isotopes enable easy localization of the labels in the products by 2 H NMR, 13C NMR, and mass spectrometry. We found that 2␣-hydroxytrichodiene is the first oxygenated step in the biosynthesis of both 3-acetyldeoxynivalenol and sambucinol. The stereoisomer 2␤-hydroxytrichodiene and 12,13-epoxytrichodiene are not biosynthetic intermediates and have not been isolated as metabolites. We also demonstrated that the dioxygenated 12,13-epoxy-9,10-trichoene-2␣-ol is a biosynthetic precursor to trichothecenes as had been suggested in a preliminary work. Its stereoisomer was not found in the pathway. A further confirmation of our results was the isolation of both oxygenated trichodiene derivatives 2␣-hydroxytrichodiene and 12,13-epoxy-9,10-trichoene-2␣-ol as natural metabolites in F. culmorum cultures.Trichothecenes are toxic secondary metabolites produced by fungi, in particular by Fusarium spp. They infect mostly wheat, grains, and corn and therefore affect human and animal health (1-4). Fusarium culmorum (HLX-1503) produces two major trichothecene metabolites (5): 3-acetyldeoxynivalenol (3-ADN) 1 and sambucinol (SOL) (Fig. 1). These mycotoxins have been known for a long time (6); however, there is not yet an efficient detoxification procedure. Since trichodiene (TDN; 1, Fig. 1), the biosynthetic precursor to trichothecenes, is not toxic, knowledge of its first oxidized metabolite will enable the design of a potent inhibitor to trichothecenes. We therefore decided to focus on the identification of the oxygenation steps after the hydrocarbon trichodiene. The first oxygenated trichodiene derivatives isolated from F. culmorum were 9,10-trichoene-12,13-diol (2d) and 12,13-epoxy-9,10-trichoene-2␣-ol (3a) (Fig. 1) (8). These compounds had been detected by the kinetic pulse-labeling method (7) and could accumulate when the inhibitor ancymidol was used (8). In addition, they had been isolated with a radiolabel after feeding (3RS)-[2-14 C]mevalonate to F. culmorum cultures and isolating and purifying the derived radiolabeled 2d and 3a. These compounds were separately fed to F. culmorum cultures, and the derived trichothecenes 3-ADN and SOL were recovered and analyzed. Metabolite 3a was found to be incorporated in both 3-ADN and SOL, whereas the trichothecenes obtained after the feeding of 2d were unlabeled. This preliminary result suggests that 3a might be a biosynthetic precursor to 3-ADN and SOL, whereas 2d is a dead end metabolite (8). This result is not extremely rigorous, since no degradation could be done...

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