BIOSYNTHESIS OF TRICHOTHECENE MYCOTOXINS - IDENTIFICATION OF ISOTRICHODIOL AS A POST-TRICHODIENE INTERMEDIATE

When cultures of Fusarium culmorum CMI 14764 were treated with the furanocoumarin xanthotoxin, trichothecene biosynthesis was suppressed, and large amounts of trichodiene accumulated, along with smaller amounts of 12,13-epoxytrichothec-9-ene (EPT) and isotrichodermin. Trichodiene was shown to be a precursor of the trichothecene mycotoxins in F. culmorum, and when large amounts of trichodiene were supplied, a new trichodiene metabolite isotrichodiol was found to accumulate. This compound, 12,13-epoxy-2-alpha,11-alpha-dihydroxytrichodiene, was shown to be a biosynthetic precursor of the trichothecenes, and represents the first demonstrated post-trichodiene intermediate in the pathway to trichothecenes. Slow, acid-catalysed cyclization of isotrichodiol to EPT was demonstrated, but the rapid in vivo incorporation into EPT points to an enzyme-catalysed process in the fungus. The biosynthesis of oxygenated trichothecenes such as 3-acetyldeoxynivalenol in F. culmorum appears to require further 3-hydroxylation to isotrichotriol prior to cyclization.