4 Conclusion
The metabolome of an organism strictly refers to all metabolites produced during its life. The Taxus metabolome, as briefly described in this chapter, relates to that part of Taxus secondary metabolism that begins with the formation of taxa-4,11-diene and ends with the production of a taxane diterpenoid, such as the pharmaceutically important drug taxol. The metabolic pathways that originate fromtaxa-4,11-diene and result in the formation of the over 400 taxoids so far described form a complex network through which taxol biosynthesis is woven. While less than 40 of these taxoids (comprising about 85 mass %) have been characterized in our plant cell cultures, most are not involved in taxol biosynthesis. Identification of the taxoids that are produced in our Taxus plant cell culture system and understanding their relationship to other intermediates in the taxol biosynthetic pathway provide clues to the order of the synthesis of intermediates and branch points in this complex metabolic grid. This knowledge is critical for the intelligent targeting of genes for future metabolic engineering of plant cell cultures for increased taxol production.
Taxol® is a registered trademark of the Bristol-Meyers-Squibb company. The approved generic term for the drug is paclitaxel. Due to historic precedent and the abundance of taxoids with names derived from “taxol,” we will use the more familiar term “taxol” when referring to this compound.
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References
Baloglu E, Kingston DGI (1999) The taxane diterpenoids. Phytochemistry 62:1448–1472
Creelman RA, Mullett JE (1997) Biosynthesis and action of jasmonates in plants. Annu Rev Plant Physiol Plant Mol Biol 48:355–381
Croteau R, Ketchum REB, Long RM, Kaspera R, Wildung MR (2006) Taxol biosynthesis and molecular genetics. Phytochem Rev 4 (in press)
Hefner J, Rubenstein SM, Ketchum REB, Gibson DM, Williams RM, Croteau R (1996) Cytochrome P450-catalyzed hydroxylation of taxa-4(5),11(12)-diene to taxa-4(20),11(12)-dien-5α-ol: the first oxygenation step in taxol biosynthesis. Chem Biol 3:479–489
Hezari M, Croteau R (1997) Taxol biosynthesis: an update. Planta Med 63:291–295
Hezari M, Lewis NG, Croteau R (1995) Purification and characterization of taxa-4(5),11(12)-diene synthase from Pacific yew (Taxus brevifolia) that catalyzes the first step of taxol biosynthesis. Arch Biochem Biophys 322:437–444
Hezari M, Ketchum RE, Gibson DM, Croteau R (1997) Taxol production and taxadiene synthase activity in Taxus canadensis cell suspension cultures. Arch Biochem Biophys 337:185–190
Itokawa H (2003) Taxoids occurring in the genus Taxus. In: Itokawa H, Lee H-K (eds) Taxus: The Genus Taxus, Taylor and Francis, London, pp 35–78
Jennewein S, Long RM, Williams RM, Croteau R (2004) Cytochrome P450 taxadiene 5α-hydroxylase a mechanistically unusual monooxygenase catalyzing the first oxygenation step of Taxol biosynthesis. Chem Biol 11:379–387
Ketchum REB, Gibson DM (1996) Paclitaxel production in cell suspension cultures of Taxus. Plant Cell Tissue Organ Cult 46:9–16
Ketchum REB, Gibson DM, Croteau RB, Shuler ML (1999a) The kinetics of taxoid accumulation in cell suspension cultures of Taxus following elicitation with methyl jasmonate. Biotechnol Bioeng 62:97–105
Ketchum REB, Tandon M, Gibson DM, Begley T, Shuler ML (1999b) Isolation of labeled 9-dihydrobaccatin III and related taxoids from cell cultures of Taxus canadensis elicited with methyl jasmonate. J Nat Prod 62:1395–1398
Ketchum REB, Luong JV, Gibson DM (1999c) Efficient extraction of paclitaxel and related taxoids from leaf tissue of Taxus using a potable solvent system. J Liq Chromatogr Relat Technol 22:1715–1732
Ketchum REB, Rithner CD, Qiu D, Williams RM, Croteau RB (2003) Taxus metabolomics: methyl jasmonate preferentially induces production of taxoids oxygenated at C-13 in Taxus x media cell cultures. Phytochemistry 62:901–909
Kingston DGI, Molinero AA, Rimoldi JM (1993) The taxane diterpenoids. Prog Chem Org Nat Prod 61:1–206
Koepp AE, Hezari M, Zajicek J, Stofer Vogel B, LaFever RE, Lewis NG, Croteau R (1995) Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the first committed step of taxol biosynthesis in Pacific yew. J Biol Chem 270:8686–8690
Miller B, Madilao LL, Ralph S, Bohlmann J (2005) Insect-induced conifer defense. White pine weevil and methyl jasmonate induce traumatic resinosis, de novo formed volatile emissions, and accumulation of terpenoid synthase and putative octadecanoid pathway transcripts in sitka spruce. Plant Physiol 137:369–382
Mirjalili N, Linden JC (1996) Methyl jasmonate induced production of taxol in suspension cultures of Taxus cuspidata: ethylene interaction and induction models. Biotechnol Prog 12:110–118
Williams DC, Wildung MR, Jin AQ, Dalal D, Oliver JS, Coates RM, Croteau R (2000) Heterologous expression and characterization of a “pseudomature” form of taxadiene synthase involved in paclitaxel (Taxol) biosynthesis and evaluation of a potential intermediate and inhibitors of the multistep diterpene cyclization reaction. Arch Biochem Biophys 379:137–146
Yukimune Y, Tabata H, Higashi H, Hara Y (1996) Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures. Nat Biotechnol 14:1129–1132
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Ketchum, R.E.B., Croteau, R.B. (2006). The Taxus Metabolome and the Elucidation of the Taxol® Biosynthetic Pathway in Cell Suspension Cultures. In: Saito, K., Dixon, R.A., Willmitzer, L. (eds) Plant Metabolomics. Biotechnology in Agriculture and Forestry, vol 57. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29782-0_21
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