Plants terpenoids

Jensen, S.R., Plant iridoids, their biosynthesis and distribution in angiosperms, in Ecological Chemistry and Biochemistry of Plant Terpenoids, Harbome, J.B. et al., Eds., Clarendon Press, Oxford, 1991, 133. 

Langenheim J H (1994), Higher plant terpenoids-aphytocentric overview of their ecological roles , J Chem Ecol, 20, 1223-1280. 

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. 

Marston, A., K. Hostettmann, J. B. Harborne, and F. A. Tomas-Barberan. 1991. Plant saponins chemistry and molluscicidal action. Ecological chemistry biochemistry plant terpenoids. Proc. Phytochem. Soc. Europe 31. p. 264-286. 

Bohlmann, J., Meyer-Gauen, G. and Croteau, R. (1998). Plant terpenoid synthases ... 

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. 

Goad, L. J. (1991) in Ecological Chemistry and Biochemistry of Plant Terpenoids (Harborne, J. 

Fischer, N.H. Plant terpenoids as allelopathic agents. In Ecological Chemistry and Biochemistry of Plant Terpenoids. Harborne, J.B. and F.A. Tomas-Barberan (Eds.). Proceedings of the Phytochemical Society of Europe. Clarendon Press-Oxford. 1991 pp. 377-398. 

Bergstrom L. G. (1991) Chemical ecology of terpenoid and other fragrances of angiosperm flowers. In Ecological Chemistry and Biochemistry of Plant Terpenoids, eds J. B. Harbome and F. A. Tomas-Barberan, pp. 287-296. Clarendon Press, Oxford. 

Bohlmann J., Meyer-Gauen G. and Croteau R. (1998) Plant terpenoid synthases molecular biology and phylogenetic analysis. Proc. Natl. Acad. Sci. USA 95, 4126-4133. Boppre M. (1984) Chemically mediated interactions between butterflies. In The Biology of Butterflies, eds R. I. Vane-Wright and P. R. Ackery, pp. 259-275. Princeton University Press, Princeton, NJ. 

Geerlings, A., Redondo, F.J., Contin, A. (2001) Biotransformation of tryptamine and se-cologanin into plant terpenoid indole alkaloids by transgenic yeast. Aprpl. Microbiol. Biotechnol, 56, 420. ... 

Mevalonic acid, the product of HMGR, is converted to IPP by the sequential action of three enzymes mevalonate kinase, phosphomevalonate kinase and diphosphomevalonate decarboxylase (Fig. 5.3). These three catalysts have not previously been considered to be important control points in plant terpenoid biosynthesis, and little new information has appeared to alter this view. The... 

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. 

Geerlings A, Redondo FJ, Contin A, MemeUnk J, Van der Heijden R, Verpoorte R. Biotransformation of tryptamine and 150. secologanin into plant terpenoid indole alkaloids by transgenic... 

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). 

Bohlmann J, Meyer-Gaven G, Croteau R. Plant terpenoid synthases molecular biology and phylogenetic analysis. Proc. Natl. Acad. Sci. USA. 1998 95 4126-4133. 

Over 20,000 terpenoids have been identihed (1), and more are being discovered continuously. Plant terpenoids are important in both primary and secondary (speciahzed) metabolism. Their importance in primary metabolism includes physiological, metabolic, and stmctural roles such as plant hormones, chloro-plast pigments, roles in electron transport systems, and roles in the posttranslational modihcation of proteins. In secondary metabolism, the roles of plant terpenoids are incredibly diverse but are associated most often with defense and communication of sessile plants interacting with other organisms. Examples include terpenoid chemicals that form physical and chemical barriers, antibiotics, phytoalexins, repellents and antifeedants against insects and other herbivores, toxins, attractants for pollinators or fruit-dispersing animals, host/nonhost selection cues for herbivores, and mediators of plant-plant and mycorrhiza interactions (2, 3). 

The combined genomics and chemical approaches to plant terpenoid research are not restricted to the few plant species for which more or less complete genome sequences are now available. The discovery of many of the genes and enzymes for the formation of terpenoids such as menthol and related monoter-penes in peppermint Mentha x piperita) (15), artemisinin in Artemisia annua (16), Taxol in the yew tree (Taxus) (17), or conifer diterpene resin acids in species of spmce (Picea ) and pine (Pinus) (18) have been possible on the foundation of highly specialized efforts of EST and full-length cDNA sequencing combined with characterization of recombinant enzymes and analysis of the terpenoid metabolome of the target plant species. 

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

Artemisinin is used here as an example of a plant sesquiterpenoid with both traditional value as well as with medicinal and social value in the twenty-first century. Research on artemisinin has also established new benchmarks for biochemical engineering and functional genomics of plant terpenoids. Artemisinin is a functionalized sesquiterpene with a unique peroxide linkage from the sweet wormwood Artemisia annua). Chinese herbalists have used it since ancient times, and it is now used for its unique efficacy to treat multidrug-resistant strains of the malaria parasite Plasmodium falciparum. Its medicinal importance has prompted studies into its biosynthesis and its biochemical engineering so that cost-effective methods for producing it in large scale and in consistent quality may be realized. 

The study of plant terpenoids shares many of the same tools for their isolation, identification, characterization, and synthesis that are required in other natural product research. Advances in separation science, analytical chemistry, spectroscopic tools, and synthetic organic chemistry all affect the study of terpenoids in plants. 

Stereochemistry often is an integral component to both the chemical structure and the biological function of plant terpenoids. For volatile terpenoids, chiral GC stationary phases (48) provide the enantiomeric separation for quantitative analysis, and, provided an authentic standard of known absolute... 

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