Phytochemistry Reviews

, Volume 5, Issue 1, pp 75–97 | Cite as

Taxol Biosynthesis and Molecular Genetics

  • Rodney Croteau
  • Raymond E. B. Ketchum
  • Robert M. Long
  • Rüdiger Kaspera
  • Mark R. Wildung
Article

Abstract

Biosynthesis of the anticancer drug Taxol in Taxus (yew) species involves 19 steps from the universal diterpenoid progenitor geranylgeranyl diphosphate derived by the plastidial methyl erythritol phosphate pathway for isoprenoid precursor supply. Following the committed cyclization to the taxane skeleton, eight cytochrome P450-mediated oxygenations, three CoA-dependent acyl/aroyl transfers, an oxidation at C9, and oxetane (D-ring) formation yield the intermediate baccatin III, to which the functionally important C13-side chain is appended in five additional steps. To gain further insight about Taxol biosynthesis relevant to the improved production of this drug, and to draw inferences about the organization, regulation, and origins of this complex natural product pathway, Taxus suspension cells (induced for taxoid biosynthesis by methyl jasmonate) were used for feeding studies, as the foundation for cell-free enzymology and as the source of transcripts for cDNA library construction and a variety of cloning strategies. This approach has led to the elucidation of early and late pathway segments, the isolation and characterization of over half of the pathway enzymes and their corresponding genes, and the identification of candidate cDNAs for the remaining pathway steps, and it has provided many promising targets for genetically engineering more efficient biosynthetic production of Taxol and its precursors.

Keywords

baccatin cytochrome P450 taxoid hydroxylases paclitaxel Taxaceae taxadiene synthase taxane diterpenoids taxoid acyl transferases taxoids Taxol Taxus yew 

Abbreviations

DD-RT-PCR

differential display of mRNA-reverse transcription-polymerase chain reaction

DMAPP

dimethylallyl diphosphate

DXP

1-deoxy-d-xylulose-5-phosphate

EST

expressed sequence tags

GGPP

geranylgeranyl diphosphate

GGPPS

geranylgeranyl diphosphate synthase

IPP

isopentenyl diphosphate

IPPI

isopentenyl diphosphate isomerase

MEP

2-C-methyl-d-erythritol phosphate

NMR

nuclear magnetic resonance spectroscopy

PAM

phenylalanine aminomutase

TS

taxadiene synthase

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Copyright information

© Springer 2006

Authors and Affiliations

  • Rodney Croteau
    • 1
  • Raymond E. B. Ketchum
    • 1
  • Robert M. Long
    • 1
  • Rüdiger Kaspera
    • 1
  • Mark R. Wildung
    • 1
  1. 1.Institute of Biological ChemistryWashington State UniversityPullmanUSA

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