The role of gut micro-organisms in the metabolism of deoxynivalenol administered to rats.

1. Oral administration of deoxynivalenol (DON) to control rats resulted in the appearance of a de-epoxy metabolite in urine and faeces. 2. When DON was administered to rats treated with antibiotics to deplete their gut microflora there was very little excretion of radioactivity as the de-epoxy metabolite in faeces or urine. 3. Incubation of DON with a strictly anaerobic preparation of gut contents resulted in the progressive appearance of de-epoxy DON during a 24 h incubation period. 4. Incubation of DON with liver homogenate did not result in the appearance of the de-epoxy DON metabolite. 5. These results indicate that the presence of de-epoxy DON in rat excreta, following the oral administration of DON, is the result of metabolism by micro-organisms in the gut.

Trichothecene mycotoxins from Fusarium culmorum cultures.

Chemical analysis of the culture filtrates of Fusarium culmorum CMI 14764 has demonstrated the presence of seven trichothecene mycotoxins. Major metabolites are 3-acetyldeoxynivalenol and 7 alpha, 8 alpha-dihydroxycalonectrin, with 3,15-diacetyldeoxynivalenol, deoxynivalenol, calonectrin, isotrichodermin and 12,13-epoxytrichothec-9-ene (EPT) as minor products. The occurrence of the rarely encountered unsubstituted trichothecene EPT is significant in that this compound may function as a common intermediate in the biosynthetic pathways to all natural trichothecenes. The structures of the known trichothecenes isolated from F. culmorum suggest a route in which EPT is sequentially oxygenated to the more complex deoxynivalenol derivatives.

Studies on the metabolism of deoxynivalenol in the rat.

The metabolism and tissue distribution of [14C]deoxynivalenol have been studied in male PVG rats. Following administration of a single oral 10-mg/kg dose, radioactivity excreted in the urine and faeces accounted, respectively, for 25 and 64% of the administered dose within 96 hr. Less than 0.15% of the dose was detected in the respired air. Very little radioactivity appeared to be retained in any of the tissues examined after 96 hr. HPLC separation of several urinary and faecal metabolites was achieved on a reversed-phase column, using two different elution systems, one at neutral pH and one acidified. Two of the major non-polar HPLC peaks were identified by gas chromatography-mass spectrometry as unchanged deoxynivalenol and 3 alpha,7 alpha,15-trihydroxytrichothec-9,12-dien-8-one.

Metabolic conversions of trichothecene mycotoxins: biotransformation of 3-acetyldeoxynivalenol into fusarenon-X.

The trichothecene mycotoxin 3-acetyldeoxynivalenol was transformed by cultures of the diacetoxyscirpenol producer Fusarium sp. strain C37410-90 into four compounds, identified as deoxynivalenol, 15-acetyldeoxynivalenol, 3,15-diacetyldeoxynivalenol and fusarenon-X. The major transformations are the result of specific esterification and de-esterification processes, but the production of fusarenon-X involves in addition a novel 4 beta-hydroxylation of the trichothecene ring system itself.

Biosynthesis of trichothecene mycotoxins in Fusarium culmorum cultures.

A high yielding production of the trichothecene mycotoxin 3-acetyldeoxynivalenol (3-AcDON) in cultures of Fusarium culmorum is described. By supplying [14C]acetate, 14C-labelled 3-AcDON suitable for further metabolic studies has been obtained. The pattern of labelling has been ascertained by using 13C-labelled acetate precursors, and is in line with established biosynthetic data. A second trichothecene produced in significant amounts by F. culmorum has been identified as 3 alpha, 15-diacetoxy-7 alpha, 8 alpha-dihydroxy-12, 13-epoxytrichothec-9-ene (7 alpha, 8 alpha-dihydroxycalonectrin).