Trichodiene, biosynthesis

Cane DE, Swanson S, Murthy PPN (1981) Trichodiene Biosynthesis and the Enzymatic Cyclization of Famesyl Pyrophosphate. J Amer Chem Soc 103 ... 

Propose a mechanism for the biosynthesis of the sesquiterpene trichodiene from famesyl diphosphate. The process involves cyclization to give an intermediate secondary carbocation, followed by several carbocation rearrangements. 

A quantum chemical investigation of the biosynthesis of farnesyl pyrophosphate through the condensation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate suggests that the mechanism is concerted, although the transition state has carbocationic character.164 Quantum chemical calculations were performed on the cyclization of the farnesyl cation to the sesquiterpene pentalenene.165 Two distinct pathways with similar activation barriers were identified, each differing from previous proposed mechanisms, and each involving unusual carbocationic intermediates. Mechanisms previously proposed for enzyme-catalysed formation of the sesquiterpene trichodiene involve carbocation intermediates with a 1,4-hydride transfer as the key step, e.g. (89) -> (90) - (91).166 Quantum chemical calculations, however, show a... 

Cane et a/.92 have re-examined the biosynthesis of trichodiene (127) by incubation of trans,trans[ -3U2,12,13-14C]farnesyl pyrophosphate (156) [3H/14C atom ratio 2 2] with a cell-free extract of Trichothecium roseum. A crystalline derivative of the trans-diol derived from the endocyclic double bond of labelled trichodiene had a... 

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),... 

Scheme 2. Biosynthesis of trichodiene (49) and trichothecolone (101) from mevalonic acid lactone (105), labelled atom <...

Desjardins AE, Plattner RD, Beremand MN (1987) Ancymidol Blocks Trichothecene Biosynthesis and Leads to Accumulation of Trichodiene in Fusarium sporotrichioides and Gibberella pulicaris. Appl Environ Microbiol 53 1860... 

Hesketh AR, Gledhill L, Marsh DC, Bycroft BW, Dewick PM, Gilbert J (1990) Isotrichodiol A Post-Trichodiene Intermediate in the Biosynthesis of Trichothecene Mycotoxins. Chem Commun 1184... 

Zamir LO, Nikolakakis A, Huang L, St-Pierre P, Sauriol F, Sparace S, Mamer O (1999) Biosynthesis of 3-Acetyldeoxynivalenol and Sambucinol. Identification of the Two Oxygenation Steps After Trichodiene. J Biol Chem 274 12269... 

Zamir LO, Devor KA, Morin N, Sauriol E (1991) Biosynthesis of Trichothecenes Oxygenation Steps Post-trichodiene. Chem Commun 1033... 

Evans R, Hanson JR (1976) Studies in Terpenoid Biosynthesis, Part XIV. Formation of the Sesquiterpene Trichodiene. J Chem Soc, Perkin Trans 1 326... 

Wagner-Meerwein rearrangements are prevalent in the biosynthesis of terpenoids and steroids [21], An example can be represented by the concerted rearrangements (1,3-hydride and 1,2-methyl shift) that lead to the biosynthesis of trichodiene, an intermediate of the terpenes verrucarin A and roridin A (Section 3.2.24) (Figure 1.18). 

CYP58 Epoxidation of o-methyl-sterigmato-cystin precursor and trichodiene C-2 hydroxylation, C12-C13 epoxidation, Cll and C3 hydroxylations Aflatoxin and trichothecene biosynthesis A. flavus, A. parasiticus , and F. gra-minearum, F. sporotrichoides [512, 836] [513, 514]... 

Takahashi-Ando N, Ochiai N, Tokai T, Ohsato S, Nishiuchi T, Yoshida M, Fujimura M, Kimura M (2008) A screening system for inhibitors of trichothecene biosynthesis hydroxylation of trichodiene as a target. Biotechnol Lett 30 1055-1059... 

Zamir LO, Devor KA, Morin N, Sauriol F (1991) Biosynthesis of trichothecenes oxygenation steps post-trichodiene. J Chem Soc Chem Comm 1033-1034 McCormick SP, Taylor SL, Plattner RD, Beremand MN (1990) Bioconversion of possible T-2 toxin precursors by a mutant strain of Fusarium sporotrichioides NRRL 3299. Appl Environ Microbiol 56 702-706... 

Both 1,4- and 1,5-hydrogen rearrangements have been discovered in the biosynthesis of sesquiterpenes and diterpenes. A 1,4-hydrogen transfer occurs in the formation of the bicarbocyclic nucleus of the trichothecane sesquiterpenes, presumably via the parent hydrocarbon trichodiene 35, 207—209). The biosynthesis of helicobasidine, a closely related cuparene-type sesquiterpene, also has a 1,4-hydrogen rearrangement step 210). 

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