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Taxol® Biosynthesis and Production: From Forests to Fermenters

  • Christopher McElroy
  • Stefan JenneweinEmail author
Chapter

Abstract

Taxol® (paclitaxel) has fascinated researchers, medical professionals, politicians and entrepreneurs for almost half a century. Its medicinal value as a potent anti-cancer compound has expanded greatly over time as new applications have been identified for the treatment of diverse indications. Knowledge of its complex biosynthesis pathway remains incomplete, with only 14 of the 19 genes well characterized. Despite this disadvantage, huge strides have been taken towards improving access to this diterpenoid compound and meeting the ever increasing demand. Productivity has increased thanks to the development of new methods, from the pioneering bark extraction techniques and complete chemical synthesis, to semi-synthesis from precursors such as baccatin III extracted from Taxus spp. plant cultures and the first attempts to produce taxol in non-native platforms. The entire pathway should be elucidated within the next decade, perhaps allowing its introduction into a host capable of gram per litre productivity. This review outlines major and recent findings related to the characterization of the taxol biosynthesis pathway, the evolution of production methods and future prospects for exploitation by metabolic engineering of a designed microbial chassis.

Keywords

Taxol Paclitaxel Taxadiene Baccatin III Taxadiene synthase Taxaceae Taxus Cytochrome P450 Metabolic engineering Biotechnology Cell culture Diterpenoids Yew Endophytes Endophytic fungi 

Abbreviations

CPRs

Cytochrome P450 reductases

DMAPP

Dimethylallyl diphosphate

DXP

1-Deoxy-D-xylulose 5-phosphate pathway

GGPP

Geranylgeranyl diphosphate

HGT

Horizontal gene transfer

IPP

Isopentenyl diphosphate

MEP

2-C-methyl-D-erythritol 4-phosphate pathway

MVA

Mevalonate pathway

P450

Cytochrome P450 dependent mono-oxygenase

Notes

Acknowledgments

The authors would like to thank Dr Richard M Twyman and Dr Birgit Orthen for assistance with the manuscript.

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute for Molecular BiotechnologyRWTH Aachen UniversityAachenGermany
  2. 2.Department of Industrial BiotechnologyFraunhofer Institute for Molecular Biology and Applied Ecology (IME)AachenGermany

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