Acid to Trichodiene

The early work on the biosynthesis of the trichothecene nucleus related to the formation of trichothecolone (101) in Trichothecium roseum and of derivatives of verrucarol (102) in Myrothecium spp. This work has been reviewed in detail (248). The more recent work has been 

Studies in which [2--mevalonic acid lactone ( mevalonate ) (105) was used as a precursor showed that three molecules were incorporated into trichothecolone (101), the label appearing at positions 4, 8, and 14 (249), The involvement of 2-rran5-6-rra -famesyldiphosphate (106) had been shown previously using C-labelled material 250), The biosynthesis thus follows a standard sesquiterpene pathway from mevalonate through famesyldiphosphate to nerolidyldiphosphate (107) (257, 252), which is then cyclised by the enzyme trichodiene synthase to the bicy-clic hydrocarbon trichodiene (49) (253). The evidence for the participation of nerolidyldiphosphate has been reviewed (254, 255). None of the possible enzyme bound intermediates has been isolated from what is shown (107, 108) as a concerted process involving a 1,4-hydride shift and two 1,2-methyl shifts (256), 

Results consistent with the same biosynthetic pathway to trichodiene have been obtained with Fusarium graminearum and F, culmorum, initially with labelled acetate (257, 97), and, conclusively, with [3,4- C2]-mevalonate (258), 

Trichodiene synthase has been obtained from T, roseum (259) and subsequently from F, sporotrichioides (260, 261) and F, sambucinum (261), the F, sporotrichioides enzyme has been characterised. Isomerisation of famesyldiphosphate to nerolidyldiphosphate is the rate-determining step in the reaction pathway (262). Factors affecting substrate recognition by the active site have been studied (263), and a number of amino-acid 

Another important application arising from the work with trichodiene synthase has been the development of Tri5 specific polymerase chain reaction-based assays for the detection of potential trichothecene-producing Fusarium species in pure culture and in contaminated grain (269,275,276). 

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