Isotrichodermol

Trichothecene 3-O-acetyltransferase encoded by a noncluster gene, TrilOl, readily converts isotrichodermol (130) into isotrichodermin (ITD, 131) (Figure 30).262 263 This acetylation step is important for the selfprotection of trichothecene-producing Fusarium species. The C-3 acetyl is also essential for subsequent biosynthetic steps to proceed. Indeed, the 7W/0/--targeted gene disruption mutant of F. sporotrichioides could not metabolize 3-hydroxytrichothecenes, but efficiently converted exogenously added ITD (131) and other C-3 acetylated intermediates into T-2 toxin.264 After ITD (131), the biosynthetic pathways are different between type A and type B trichothecenes. 

Figure 30 Biosynthesis of Fusarium trichothecenes. In trichothecene-producing Fusarium species, one additional oxygen is added to ITdiol (128) to give isotrichotriol (129). Cyclization of isotrichotriol (129) to isotrichodermol (130) under acidic condition assumes a transient intermediate, which can also undergo isomerization to trichotriol260 and its 9a-epimer.261 Acetylation at C-3 of isotrichodermol (130) to ITD (131) is an essential step for the biosynthesis of Fusarium trichothecenes.

Isotrichodiol (53) and isotrichotriol (59) and their respective products of acid-catalysed aUylic rearrangement, trichodiol (55) and 9-epitricho-diol (56), both isolated from T. roseum, and trichotriol (63) and 9-epitrichotriol (64), isolated only from Fusarium spp., are central to the pathway from trichodiene to the epoxytrichothecene nucleus. The conversion of trichodiol and trichotriol into 12,13-epoxytrichothecene (73) and isotrichodermol (74), respectively, proceeds spontaneously, though slowly, at acid pH (152) by mechanism (A), Scheme 3. However, the rapid in vivo incorporation indicates an enzyme-mediated process (282). An alternative proposal, with mechanism (B), has isotrichodiol and isotrichotriol as the true intermediates (231). 

Although isotrichodermol (114) [or its acetate isotrichodermin (115)] was found to be a precursor both of 3-acetylvomitoxin (104) in F. culmorum (226), and of T-2 toxin (103) using the blocked mutant strain (see above) of F. sporotrichioides (232), 12,13-epoxytrichothecene (109) was not (285) (232). 12,13-Epoxytrichothecene was not converted into isotrichodermol by F. culmorum (285), and neither trichodermol (110) nor 15-hydroxy-12,13-epoxytrichothecene were precursors of T-2 toxin in F. sporotrichioides (232). These results reinforce the earlier conclusion (above) that 3a-hydroxylation of trichodiol precedes the cyclization step in these organisms. The conversion of isotrichodermol to isotrichodermin by an acetyltransferase is discussed in connection with the function of the resistance gene TrilOl (Section 3.1.4.). 

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