Terpene Biosynthesis in Plants

The diterpene taxol is used as a potent chemotherapeutic agent in cancer treatment. The hmited supply of the drug from the natural source, the bark of the Pacific Yew (Taxus brevifolia), was overcome by a semisynthetic approach. Taxol is presently manufactured by coupling the advanced naturally occurring taxoid 10-deacetylbaccatin 111, isolated from needles of the more abundant Tdxus baccata, to a synthetic side-chain precursor. 

Taxadiene undergoes an extended series of oxygenation and acylation reactions to yield taxol. So far, 8 out of 20 enzymatic steps have been in vitro catalyzed through cloned cDNAs [53]. Several regioselective CoA thioester-dependent acyltransferases, including a C13-side-chain N-benzoyltransferase which predominantly forms one 3 -epimer of 2 -deoxytaxol, are involved in the synthesis. This indicates that there is still a long way to go before taxol could be produced in microorganisms from a reconstituted biosynthesis. 

The presented examples show that it is possible to assign some general rules for the introduction of stereocenters in the biosynthesis of natural products. For this, natural products need to be grouped according to their mode of biosynthesis 

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Mahmoud, S. S., and R. B., Croteau. 2002. Strategies for transgenic manipulation of mono-terpene biosynthesis in plants . Trends Plant Sci. 7(8) 366-73. 

Fig. 26 Schematic overview of terpene biosynthesis in plants. DMAPP, dimethylallyl diphosphate DXP, desoxyxylulose phosphate FPP, famesyl diphosphate GGPP, geranylgeranyl diphosphate GPP, geranyl diphosphate IPP, isopentenyl diphosphate MVA, mevalonate...

Natural Products as Inducers of Insect Resistance. Plant growth regulators have been shown to increase the biosynthesis of certain secondary plant constituents that in turn decrease plant attack by insects. -Naphthaleneacetic acid, for example, elicits increased terpene biosynthesis in citrus, thus decreasing attack by fruit flies. The approach of using both natural and synthetic plant growth regulators may continue to find applications in insect control. 

In their efforts to study the mechanism of terpene synthases, Coates and coworkers synthesized aza derivatives of ent-kaurene. The two heterocyclic analogs, 16-aza-trachylobane (107) and 16-aza-beyerane (108), were synthesized froment-beyeran-16-one (103), which was obtained from the natural product stevioside (102, Scheme 5.24T These analogs were assessed for their utility as active site probes for various ent-diterpene cyclases and as selective inhibitors of gibberellin biosynthesis in plants. 

Figure 3.2 Schematic representation of terpene biosynthesis in higher plant cells. Blocks represent 5-carbon isoprenyl units (IPP or DMAPP).

Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

The terpenes, carotenoids, steroids, and many other compounds arise in a direct way from the prenyl group of isopentenyl diphosphate (Fig. 22-1).16a Biosynthesis of this five-carbon branched unit from mevalonate has been discussed previously (Chapter 17, Fig. 17-19) and is briefly recapitulated in Fig. 22-1. Distinct isoenzymes of 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) in the liver produce HMG-CoA destined for formation of ketone bodies (Eq. 17-5) or mevalonate.7 8 A similar cytosolic enzyme is active in plants which, collectively, make more than 30,000 different isoprenoid compounds.910 However, many of these are formed by an alternative pathway that does not utilize mevalonate but starts with a thiamin diphosphate-dependent condensation of glyceraldehyde 3-phosphate with pyruvate (Figs. 22-1,22-2). 

Steroid and Triterpene Biosynthesis Terpenes, Biosynthesis of Terpenoids in Plants ... 

In contrast to the above-ground organs of plants, roots represent an unexplored area of terpene biosynthesis and function. To date, just a small number of terpene synthases have been identified in plant roots. In Arabidopsis, the terpene synthase genes that encode 1,8-cineole synthase and (Z)-y-bisabolene synthase are expressed differentially in the stele of younger root growth zones and in the cortex and epidermis of older roots (reviewed... 

Many aroma compounds in fruits and plant materials are derived from lipid metabolism. Fatty acid biosynthesis and degradation and their connections with glycolysis, gluconeogenesis, TCA cycle, glyoxylate cycle and terpene metabolism have been described by Lynen (2) and Stumpf ( ). During fatty acid biosynthesis in the cytoplasm acetyl-CoA is transformed into malonyl-CoA. The de novo synthesis of palmitic acid by palmitoyl-ACP synthetase involves the sequential addition of C2-units by a series of reactions which have been well characterized. Palmitoyl-ACP is transformed into stearoyl-ACP and oleoyl-CoA in chloroplasts and plastides. During B-oxi-dation in mitochondria and microsomes the fatty acids are bound to CoASH. The B-oxidation pathway shows a similar reaction sequence compared to that of de novo synthesis. B-Oxidation and de novo synthesis possess differences in activation, coenzymes, enzymes and the intermediates (SM+)-3-hydroxyacyl-S-CoA (B-oxidation) and (R)-(-)-3-hydroxyacyl-ACP (de novo synthesis). The key enzyme for de novo synthesis (acetyl-CoA carboxylase) is inhibited by palmitoyl-S-CoA and plays an important role in fatty acid metabolism. 

MARTIN, D.M., GERSHENZON, J., BOHLMANN, J., Induction of volatile terpene biosynthesis and diurnal emission by methyl jasmonate in foliage of Norway spruce.. Plant Physiol, 2003, 132, 1586-1599. 

DUDAREVA, N., MARTIN, D., KISH, C.M., KOLOSOVA, N., GORENSTEIN, N., FALDT, J., MILLER, B., BOHLMANN, J. ( )-p-Ocimene and myrcene synthase genes of floral scent biosynthesis in snapdragon Function and expression of three terpene synthase genes of a new terpene synthase subfamily. Plant Cell,... 

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