Tetraterpene biosynthesis

The biosynthesis of squalene is similar to that of phy toene in tetraterpene biosynthesis, except that in the final step, a double bond is formed by elimination in tetraterpenes, whereas a hydride from NADPH is added in triterpene biosynthesis (Poulter, 1990). 

It does not appear that lycopersene (13), a tetraterpene homologous to squalene, is an intermediate in tetraterpene biosynthesis (Bramley, 1985). This compound does, however, occur in a number of organisms including carrot roots. In most plants that have been studied, 15-Z-phytoene (7,8,1 l,12,7, 8Mr,12 -octahydro-i i,il -carotene) (11) is the predominant form, although in some bacteria the 15-E form (12) is most common (Spurgeon and Porter, 1983). 

The biosynthesis of monoterpenes, the major components of peppermint essential oils, can be divided into four stages (Fig. 9.4). Stage 1 includes the formation of isopentenyl diphosphate (IPP) and dimethylallyl alcohol (DMAPP). In plants, two separate pathways are utilized for the synthesis of these universal C5 intermediates, with the cytosolic mevalonate pathway being responsible for the formation of sterols and certain sesquiterpenes, and the plastidial mevalonate-independent pathway being involved in the biosynthesis of isoprene, monoterpenes, certain sesquiterpenes, diterpenes, tetraterpenes, as well as the side chains of chlorophyll and plastoquinone.16 In peppermint oil gland secretory cells, however, the mevalonate pathway is blocked and the biosynthesis of monoterpenoid essential... 

Terpenoids are derived from the cytosolic mevalonate pathway or from the plastidial 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway (see also Terpenoid Biosynthesis). Both pathways lead to the formation of the C5 units isopentenyl diphosphate and its allylic isomer dimethylallyl diphosphate, which are the basic terpenoid biosynthesis building blocks (Fig. 1). Although increasing evidence suggests that exchange of intermediates occurs between these compartments, the cytoplasmic mevalonate pathway is generally considered to supply the precursors for the production of sesquiterpenes and triterpenes (including sterols) and to provide precursors for protein prenylation and for ubiquinone and heme-A production in mitochondria. In the plastids, the MEP pathway supplies the precursors for the production of isoprene, monoterpenes, diterpenes (e.g., GAs), and tetraterpenes (e.g., carotenoids). 

Tetraterpenes or carotenoids are synthesized from mevalo-nate precursors. Those involved in photosynthesis are synthesized in the chloroplast, but the enzymes specific for carotenoid biosynthesis are encoded in the nucleus, synthesized in cytoplasmic ribosomes, and transported into the chloroplast (Britton, 1993). Chloroplasts at different stages in development seem to differ in their ability to synthesize carotenoids autonomously from CO2 or by importation of isopentenyl pyrophosphate (isopentenyl diphosphate) (Britton, 1993). 

C. represent a major class of natural pigments, occurring widely in plants and animals. In animals they occur mainly in surface tissues such as skin, shells, scales, feathers and beaks, but also in birds egg yolks and as visual pigments. C. in animals are all of plant origin, as animals are incapable of their de novo synthesis. However, animals do convert plant C into other forms, e.g. carotenes are oxidized to vitamin A. For C. biosynthesis, see Tetraterpenes. 

PhytoAuen an aliphatic polyisoprenoid hydrocarbon carotenoid, Af, 548. P. contains ten double bonds (five of them conjugated), six branch methyl groups and two terminal isopropylidene groups. As in phytoene, the central double bond between Cl 5 and C16 has cis configuration. P. is found widely in plants, e.g. tomatoes and carrots, and it is an intermediate in lycopene biosynthesis (see Tetraterpenes). 

As artemisinin has a terpenic structure, its biosynthesis starts in the formation of isopentenyl diphosphate GPP)> as in all the natural terpenoids. In plants, IPP is synthesized either via the mevalonate pathway in the cytosol or via the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in the plastid. The IPP derived from the mevalonate pathway is generally used in the biosynthesis of sesquiterpenes (such as artemisinin), phytosterols, and triterpenes, and the IPP derived from the non-mevalonate pathway is employed in the biosynthesis of monoterpenes, diterpenes, and tetraterpenes (Fig. 89.15). 

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])...

Most of the natural carotenoid pigments are tetraterpenes, being formed from two C20 geranylgeranyl pyrophosphate units through phytoene 4.122). The mechanism of phytoene formation has much in common with squalene biosynthesis. In particular, head-on fusion of the two C20 units occurs via prephytoene pyrophosphate 4.120), analogous to presqualene pyrophosphate 4.48) formation from two... 

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