Diterpenes metabolism

Figure 10.2 Anti-sense or co-suppression of a putative P4S0 enzyme involved in diterpene metabolism in tobacco results in reduced levels of cembratriene-diols, increased levels of cembratrien-ol, and decreased colonization by aphids.1...

Hamburger B, Ohnishi T, Hamberger B, Seguin A, Bohlmann J (2011) Evolution of diterpene metabolism sitka spruee CYP720B4 eatalyzes multiple oxidations in resin aeid biosynthesis of conifer defense against insects. Plant Physiol 157 1677-1695... 

In plant plastids, GGPP is formed from products of glycolysis and is eight enzymatic steps away from central glucose metabolism. The MEP pathway (reviewed in recent literature - ) operates in plastids in plants and is a preferred source (non-mevalonate) of phosphate-activated prenyl units (IPPs) for plastid iso-prenoid accumulation, such as the phytol tail of chlorophyll, the backbones of carotenoids, and the cores of monoterpenes such as menthol, hnalool, and iridoids, diterpenes such as taxadiene, and the side chains of bioactive prenylated terpenophe-nolics such as humulone, lupulone, and xanthohumol. The mevalonic pathway to IPP that operates in the cytoplasm is the source of the carbon chains in isoprenes such as the polyisoprene, rubber, and the sesquiterpenes such as caryophyllene. 

The metabolism of taxol by Eucalyptus perriniana cell suspension cultures has been recently reported to induce hydrolyses of ester bonds at C-13, C-10 and C-2 [222]. At this moment only very few data have been published about the microbial metabolism of taxoid compounds only site specific hydrolyses of acyl side-chains at C-13 or C-10 by extracellular and intracellular esterases of Nocar-dioides albus SC13,911 and N. luteus SC13,912, respectively, have been reported [223]. On the other hand, Hu et al. [224-226] have recently described some fungal biotransformations of related natural taxane diterpenes extracted from Chinese yews or their cell cultures, in order to obtain new active substances or precursors for hemisynthesis. The taxadiene 145, a 14 -acetylated derivative... 

Overall, however, the immensity of temperate land corresponds to a most various secondary metabolic production, different from that of tropical land. The most renowned alkaloids belong to the morphine class (Chart 6.2.A1), and, in combination with isoprenoids, to the ergot and triterpene classes (Chart 6.2. A2). Prominent in the peptides are the cyclosporins (the first of which was isolated from a fiingus collected in Norway), streptogramins, and P-lactams (Chart 6.2.P). The isoprenoids are represented by pyrethrin monoterpenes, cedrane sesquiterpenes, ginkgolide and taxane diterpenes, ophiobolane sesterterpenes, and arborane and amyrin-like triterpenes (Chart 6.2.1). In the polyketides, epothilones, recently discovered from Myxobacteria, and the long known rapamycin, are two prominent classes of macrolides (Chart 6.2.FA/PO/C). 

Gershenzon, J. and Croteau, R. (1993). Terpenoid biosynthesis the basic pathway and formation of monoterpenes, sesquiterpenes and diterpenes. In Lipid Metabolism in Plants, ed. T. S. Moore Jr, pp. 339-388. Boca Raton, FL CRC Press. 

Metabolism studies are essential for approval of any clinically useful drug. Microorganisms have been successfully used as in vitro models for prediction of mammalian drug metabolism due to the significant similarity of certain microbial enzyme systems, specifically fungi, with mammalian liver enzyme systems.66 The following metabolism study represents the first for a cembranoid diterpene and may aid future development of other cembranoids as clinically useful drugs. 

To date over 30 plant terpenoid synthases have been cloned as cDNAs, and many of these were found to encode enzymes of secondary metabolism (43). Isolation and analysis of six genomic clones encoding monoterpene ((—)-pinene and (—)-limonene), sesquiterpene ((E)-a-bisabolene and S-selinene) and diterpene (abietadiene) synthases from Abies grandis, and a diterpene (taxadiene) synthase from Taxus brevifolia have been reported (44). Overexpression of a cotton farnesyl diphosphate synthase (EPPS) in transgenic Artemesia annua has resulted in 3- to 4-fold increase in the yield of the sesquiterpenoid anti-malarial drug, artemisinin, in hairy roots (45). 

When guayule is in an active growth phase, it produces little or no rubber, but if the plants are stressed, such as in cool weather or because of reduced moisture supply, biomass growth slows and the photosynthetic products are diverted to rubber production. The rubbers are not metabolized by the plant, even when it is deprived of all carbohydrates and other energy sources, and continue to accumulate for at least 10 years. The resins, which include terpenes, sesquiterpenes, diterpenes, glycerides, and low-molecular-weight polyiso-prenes, are found in resin ducts throughout the plant they constitute 10-15 dry wt % of the plant. 

The importance of dietary compounds in the determination of the metabolic profile of Chromodoris species is illustrated by the presence of a rearranged diterpene- chromodorolide A [7 0] from the Indian Ocean s nudibranch Chromodoris cavae (60). A subsequent study of a second... 

Cyclization between C-6 and C-11 is an unusual skeletal characteristic of diterpenes (Figure 3), with only four marine species reported to utilize this pattern in secondary metabolism. 

Sclareol, a natural product first isolated from the essential oil of Salvia sclarea L. (Labiatae) in 1931, is used for diverse applications in the perfumery and flavoring industries and in folk medicine. This diterpene has been described recently to be hydroxylated by three strains, i.e. Cunninghamella sp., Septomyxa affinis 66 and Mucor plumbeus 67, 68, leading essentially to hydroxylation reactions on the A ring of this compound (Fig. 16.1-12). Some of these metabolites could be used for further synthesis of some biologically active targets or as mammalian metabolism models. 

GERSHENZON, J., KREIS, W., Biosynthesis of monoterpenes, sesquiterpenes, diterpenes, sterols, cardiac glycosides and steroid saponins, in Biochemistry of Plant Secondary Metabolism, Annual Plant Reviews, Vol. 2 (Wink, M., ed,), Sheffield Academic Press, Sheffield. 1992, pp. 222-299. 

MeJA has also been used successfully in other gymnosperm systems to induce secondary metabolism and defense responses. In species of Taxus, enzymes involved in the synthesis of the diterpene taxol are induced by MeJA in suspension cultures. Studies in white spruce seedlings and cell cultures have shown that MeJA treatment induces the expression of a 14-3-3 protein and chalcone synthase. MeJA application assists ectomycorrhizal colonization of Norway spruce roots, and MeJA application to Norway spruce seedlings also enhances their survival rate when they were challenged by Pythium ultimun In recent work with Sitka spruce, we have established comprehensive gene expression profiles of... 

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