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Taxol® Biosynthesis and Production: From Forests to Fermenters

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Biotechnology of Natural Products

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.

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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

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Acknowledgments

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

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Authors and Affiliations

  1. Institute for Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany

    Christopher McElroy

  2. Department of Industrial Biotechnology, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Forckenbeckstrasse 6, 52074, Aachen, Germany

    Stefan Jennewein

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  1. Biotechnology of Natural Products, Technische Universität München, Freising, Germany

    Wilfried Schwab

  2. Institute of Biological Chemistry and M.J. Murdock Metabolomics Laboratory, Washington State University, Pullman, Washington, USA

    Bernd Markus Lange

  3. Bioanalytics, Institute of Nutritional and Food Sciences (IEL), University of Bonn, Bonn, Germany

    Matthias Wüst

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McElroy, C., Jennewein, S. (2018). Taxol® Biosynthesis and Production: From Forests to Fermenters. In: Schwab, W., Lange, B., Wüst, M. (eds) Biotechnology of Natural Products. Springer, Cham. https://doi.org/10.1007/978-3-319-67903-7_7

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