Plants terpenoid pathways

The late cannabinoid pathway starts with the alkylation of ohvetolic acid (3.2 in Fig. 4) as polyketide by geranyl diphosphate (3.1) as the terpenoid unit. Terpenoids can be found in all organisms, and in plants two terpenoid pathways are known, the so called mevalonate (MEV) and non-mevalonate (DXP) pathway as described by Eisenrich, lichtenthaler and Rohdich [23,24,29,30]. The mevalonate pathway is located in the cytoplasm of the plant cells [30], whereas the DXP pathway as major pathway is located in the plastids of the plant cells [29] and delivers geranyl diphosphate as one important precursor in the biosynthesis. 

Much attention has been paid to the last step of the formation of monoter-penes and sesquiterpenes, which is catalysed by terpenoid synthases. Over 30 complementary DNAs (cDNAs) encoding plant terpenoid synthases involved in the primary and secondary metabolism have been cloned, characterised, and the proteins heterologously expressed [6]. However, because geranyl diphosphate and farnesyl diphosphate are not readily available substrates, their biotransformation by terpenoid synthases is not economically viable. As a result, considerable effort has been put into engineering the total plant terpenoid biosynthetic pathway in recombinant microorganisms. 

In the 1970s the biosynthesis of cannabinoids was investigated with radiolabeling experiments. 14C-labeled mevalonate and malonate were shown to be incorporated into tetrahydrocannabinolic acid and cannabichromenic acid at very low rates (< 0.02%). Until 1990 the precursors of all terpenoids, isopentenyl diphosphate and dimethyl-allyl diphosphate were believed to be biosynthesized via the mevalonate pathway. Subsequent studies, however, proved that many plant terpenoids are biosynthesized via the recently discovered deoxyxylulose phosphate pathway (Eisenreich et al., 1998 Rohmer, 1999). It was shown that the Cio-terpenoid moiety of cannabinoids is biosynthesized entirely or predominantly (>98%) via this pathway (Fellermeister et al., 2001). The phenolic moiety is generated by a polyketide-type reaction sequence. 

The prenyltransferases that catalyse the s)mtheses of GPP, FPP and GGPP may be important regulatory enz)mies in plant terpenoid bios)mthesis since they are situated at the primary branch points of the pathway, directing flux among the various major classes of terpenoids. The level of prenyltransferase activity is, in fact, closely correlated with the rate of terpenoid formation in many experimental systems (Dudley et at, 1986 Hanley et at, 1992 Hugueney et at, 1996) consistent with the regulatory importance of these catalysts. The localization of specific prenyltransferases in particular types of tissue or subcellular compartments may control the flux and direction of terpenoid synthesis at these sites. For example, the GPP synthase in Salvia officinalis is restricted to the secretory cells of the glandular trichomes, which are the sole site of monoterpene bios)mthesis in this species (Croteau and Purkett, 1989). 

Cartayrade, A., Schwarz, M., Jaun, B. and Arigoni, D. (1994) Detection of two independent mechanistic pathways for the early steps of isoprenoid biosynthesis in Ginkgo biloba, in Second Symposium of the European Network on Plant Terpenoids. Strasbourg, France. 

Figure 1 The two pathways to the universal precursors of plant terpenoids.

Overexpression of the MEP pathway toward improved production of plant terpenoids of economic value... 

The MEP pathway is the starting material of major plant terpenoids of economic value e.g., monoterpenes from essential oils, diterpenoids with potent biologic activity (taxol, ginkgolides), vitamins (tocopherol), or vitamin precursors (carotenoids). The first attempts to overexpress some of its genes (especially dxs or dxr) led to enhanced carotenoid production in tomato (18) or monoterpenes in mint (19). 

Information on derivatives of the alkaloidal types considered so far is as follows (o) there is good evidence that the biosynthesis of strychnine (51) in Strychnos nux vomica plants follows the terpenoid pathway and it is proved that carbons x and y of (51) are derived from acetate the Wieland-Gumlich aldehyde (52) is not incorporated into strychnine by these plants b) apparicine... 

Radioactive tracer work has shown that nomilin (3) is biosynthesized by the terpenoid pathway from acetate in the phloem region of stems and translocated to other parts of plants such as leaves, fruit tissues and seeds (13,14). At those locations, nomilin is further biosynthesized to other limonoids. Limonoid biosynthesis occurs at each location independently, thus the composition of limonoids in fruit tissues, seeds and leaves are different from each of the others. Limonin is biosynthesized from nomilin via obacunone (4), obacunoate (5) and ichangin (6) (15-17) (Fig. 2)... 

As similar pathways may be differently regulated in different species, and as one cannot extrapolate findings for one plant to another plant, we particularly focus on the regulation of the biosynthesis of terpenoid indole alkaloids in C. roseus. Even within one plant the pathway might be differently regulated in different tissues. Findings from related plant species thus are not fully covered only where necessary is a comparison made of C. roseus with related plant species. 

Lewinsohn, E., Schalechet, F.,Wilkinson, J., Matsni, K.,Tadmor,Y., Nam, K.H., Amar, O., Lastochkin, E., Larkov, O., Ravid, U., Hiatt, W. et al.. Enhanced levels of the aroma and flavor compound S-linalool by metabolic engineering of the terpenoid pathway in tomato fruits. Plant Physiol., 127, 1256, 2001. 

Nomilin the general biosynthetic precursor of all limonoids, is biosynthesized via the terpenoid pathway from acetate and/or mevalonate in stems. Nomilin is then translocated to other plant tissues, including leaves, seeds, and fruit tissues, where it is converted to the other limonoids independently (Hasegawa et al. 1986 Ou et al. 1988). In most citrus species and hybrids, nomilin is converted to obacunone and then to obacunoate. Obacunaote is then converted to limonin probably via the intermediate ichangin. Nomilinic acid is the predominant acidic limonoid in citrus, but it does not seem to be directly involved in the biosynthetic pathways of major limonoids. 

Lewinsohn, E., etak (2001) Enhanced levels of the aroma and flavor compound S-linalool by metabolic engineering of the terpenoid pathway in tomato fruits. Plant Physiol. 127, 1256-1265... 

The terpenoid precursor isopentenyl diphosphate, formerly called isopentenyl pyrophosphate and abbreviated IPP, is biosynthesized by two different pathways depending on the organism and the structure of the final product. In animals and higher plants, sesquiterpenoids and triterpenoids arise primarily from the mevalonate pathway, whereas monoterpenoids, diterpenoids, and tetraterpenoids are biosynthesized by the 1-deoxyxylulose 5-phosphate (DXP) pathway. In bacteria,... 

Eicosanoids and terpenoids are still other classes of lipids. Eicosanoids, of which prostaglandins are the most abundant kind, are derived biosynthetically from arachidonic acid, are found in all body tissues, and have a wide range of physiological activity. Terpenoids are often isolated from the essential oils of plants, have an immense diversity of structure, and are produced biosynthetically from the five-carbon precursor isopentenyl diphosphate (IPP). lsopentenyl diphosphate is itself biosynthesized from 3 equivalents of acetate in the mevalonate pathway. 

Rodriguez-Concepcion, M. and Boronat, A., Elncidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in hacteria and plastids a metabolic milestone achieved throngh genomics. Plant Physiol. 130, 1079, 2002. Rodriguez-Concepcion, M., Early steps in isoprenoid biosynthesis multilevel regulation of the supply of common precursors in plant cells, Phytochem. Rev. 5, 1, 2006. Eisenreich, W., Rohdich, F., and Bacher, A., Deoxyxylulose phosphate pathway to terpenoids, Trends Plant Sci. 6, 78, 2001. 

Many phytotoxic compounds produced by higher plants are phenolic compounds. Several of these have been implicated in allelopathy. Based on the biosynthetic pathway from which they are derived, phenolic compounds produced by higher plants fall into two general categories 1) terpenoid phenolic compounds derived from five... 

---