Dimethylallylpyrophosphate

The addition of mevalonic acid-l-C14 to a pyroclavine- and festuclavine-producing fungus strain yielded inactive alkaloids which, in agreement with the scheme, showed that the carboxyl group of the mevalonic acid is not incorporated. Lowering of the assimilation of mevalonic acid-2-C14 by the addition of dimethylallylpyrophosphate or isopentenylpyrophos-phate supported the assumption that mevalonic acid enters the alkaloid molecule via one of these activated isoprene radicals. This was confirmed by the incorporation of deuterated isopentenylpyrophosphate in alkaloids of the clavine type in saprophytic cultures of a Claviceps strain (128). 

AcetylCoA (C2) can also react with acetoacetylGoA (Cj) to generate hydroxy-methylglutarylCoA (HMGCoA) (C6) and thence the isoprenoid precursor mevalonate (C6). Mevalonate (C(i) ultimately yields the key C-, isoprenoids isopentenylpyrophosphate (CH3G(=GH2)—CH2—CH2—O—P03—P03) (IP-PP) and dimethylallylpyrophosphate (CH3— C(GH3)=GH—CH2—O—P03—P03) (DMA-PP), the immediate precursors of cholesterol and... 

The formation of ergot alkaloids from L-tryptophan is well-known (Herbert, 1989 Groeger and Floss, 1998 Markert et al., 2008). L-Tryptophan condenses with dimethylallylpyrophosphate (DMAPP) to give y,y-dimethylallyltryptophan (DMAT), which is modified via chanoclavine 1 to give agroclavine and finally elymoclavine (Fig. 2.14). Lysergic acid maybe formed from this last alkaloid. 

Dhillon, D.S. and Brown, S.A. (1976) Localization, purification and characterization of dimethylallylpyrophosphate umbeUiferone dimethylallyl transferase from Ruta graveolens. Arch. Biochem. Biophys., 177, 74-83. 

Dimethylallylpyrophosphate (DMAPP) originating from cytosolic mevalonate (JVIVA) pathway probably serves as a precursor of tRNA isoprenylation [80]. Release of cytokinins via tRNA degradation could at least serve as a possible source of cA-zeatin, which is much more abundant in RNA than the tran5-isomer [89] and further de novo biosynthesis of this cytokinin species [90] as well as its isomerization from trans-xQ-dim have not been proved yet. 

Heinstein PF, Lee S-L, Floss HG. Isolation of dimethylallylpyrophosphate tryptophan dimethylallyltransferase from the ergot fungus (Claviceps spec.). Biochem Biophys Res Commun 44 1244-1251, 1971. 

The biosynthesis of the furan moiety was investigated for skimmianine, a dictamnine-related alkaloid, using Fagara coco (Rutaceae). Thus, when C-4- or C-5-labeled 3R-mevalonic acid was used in the biosynthetic pathway, C-labeled skimmianine was observed in both cases. When the labeled skimmianine was degraded, radioactive skimmianic acid was obtained from C-4-labeled 3R-mevalonic acid, but radioinactive skimmianic acid was obtained when C-5-labeled 3R-mevalonic acid was fed. Consequently, it was concluded that the C-T and C-2 carbons (furan moiety) of skimmianine were derived from the C-5 and C-4 carbons of mevalonic acid, respectively [4].The biosynthetic precursor of dictamnine is therefore a quinoline alkaloid with a prenyl moiety, derived from dimethylallylpyrophosphate (DMAPP), at the C-3 position, such as platy-desmine [5]. It was also shown that the methyl carbon of the methoxyl moiety at the C-4 position of skimmianine was derived from methionine. 

A similar mechanism was also postulated by Barrow et al. for the incorporation of the reversed isoprene unit at the indolic 3-position of roquefortine (see Schemes 22 and 25) [44] to date there is no experimental support published in the literature for the notion that the reverse prenyl unit at ei er the 2-position, as is found in echinulin, or the 3-position, as is found in roquefortine, is introduced indirectly at the indole nitrogen (or some other position) followed by migration. All evidence, both direct and indirect, points to the direct S attack of the pertinent indole carbons on dimethylallylpyrophosphate. 

Fig. 95.1 Terpene biosynthesis pathways and their subcellular localization in the plants. Different classes of terpenes are respectively formed in the cytosol or the plastid by two independent pathways in the plants, that is, acetate-mevalonate pathway (MEV) (cytosol) and methylerythritol 4-phosphate (MEP) or deoxyxylulose 5-phosphate pathway (DXP) (plastid). Mraioterpcmes, diterpenes, and tetraterpenes are derived from IPP and DMAPP Irran the plastidial MEP ot DXP pathway. Sesquiterpenes and triterpenes are biosynthesized from IPP and DMAPP from the cytosol pathway. Black square with a white question mark suggests a possible transport of IPP (isopentenylpyrophosphate) from the plastid to the cytosol. Other metabolites involved in the different steps are DMAPP dimethylallylpyrophosphate, FPP famesylpyrophosphate, GASP D- glyceraldehyde- 3-phosphate, GPP geranylpyrophosphate, GGPP geranylgeranylpyro-phosphate. TPSs in the circle correspond to terpene synthases. Broken arrows show several enzymatic steps (Adapted from Aharoni et al. [8] and Sallaud et al. [154])...

The enzyme responsible for condensation of L-tryptophan and DMAPP is dimethylallylpyrophosphate L-tryptophan dimethylallyl transferase (DMAT synthase). It has been isolated by the group of Floss and these investigators also purified it to homogeneity and performed the first characterisations (Heinstein et al., 1971 Lee et ai, 1976). Initially, the enzyme was reported to be a monomeric... 

Lee, S.L., Floss, H.G. and Heinstein, P. (1976) Purification and properties of dimethylallylpyrophosphate tryptopharm dimethylallyl transferase, the first enzyme of ergot alkaloid biosynthesis in Claviceps. sp. SD 58. Arch Biochem Biophys., 77, 84-94. 

Ellis, B. E., and S. A. Brown Isolation of Dimethylallylpyrophosphate Umbelli-ferone Dimethylallyl Transferase from Ruta graveolens. Canad. J. Biochem. 52, 734... 

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