Skip to main content

The Taxus Metabolome and the Elucidation of the Taxol® Biosynthetic Pathway in Cell Suspension Cultures

  • Chapter

Part of the book series: Biotechnology in Agriculture and Forestry ((AGRICULTURE,volume 57))

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.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Baloglu E, Kingston DGI (1999) The taxane diterpenoids. Phytochemistry 62:1448–1472

    CAS  Google Scholar 

  • Creelman RA, Mullett JE (1997) Biosynthesis and action of jasmonates in plants. Annu Rev Plant Physiol Plant Mol Biol 48:355–381

    Article  PubMed  CAS  Google Scholar 

  • Croteau R, Ketchum REB, Long RM, Kaspera R, Wildung MR (2006) Taxol biosynthesis and molecular genetics. Phytochem Rev 4 (in press)

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hezari M, Croteau R (1997) Taxol biosynthesis: an update. Planta Med 63:291–295

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Ketchum REB, Gibson DM (1996) Paclitaxel production in cell suspension cultures of Taxus. Plant Cell Tissue Organ Cult 46:9–16

    CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kingston DGI, Molinero AA, Rimoldi JM (1993) The taxane diterpenoids. Prog Chem Org Nat Prod 61:1–206

    CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

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

Download citation

Publish with us

Policies and ethics