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Metabolic Engineering for Improving Production of Taxol

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Transgenesis and Secondary Metabolism

Part of the book series: Reference Series in Phytochemistry ((RSP))

Abstract

Taxol (generic name paclitaxel), a complex diterpenoid, is an efficient antineoplastic drug extracted from the plant. It has been approved for the management of several cancers including lungs, breast, and ovary cancers. The bark of several Taxus species is the natural source of taxol, but its lower accumulation (0.01–0.04% dry weight) elevated the price of extraction. Its complex structure prohibits the complete chemical synthesis of the compounds in economical approach at the industrial level. Therefore, a plethora of approaches has been implemented by several researchers for alternative and economical production of taxol. The advent of recombinant DNA technologies has resulted in the commencement of metabolic engineering as an effective alternative for the production of pharmaceutically important plant natural products at industrial levels. Plants have emergence as a perfect system for metabolic engineering due to its relatively cheap price and easiness in growing. Plant cell factories provide an alternative source for the scale-up of the production of high added value secondary metabolites including the anticancer drug taxol that is biosynthesized in Taxus spp. in very tiny quantity. The demand for taxol and its derivatives has increased enormously owing to its unique antineoplastic activity, lack of the taxane ring in nature and complexity of chemical synthesis. Therefore, countless efforts have been executed in worldwide for the biotechnological production of taxol. In this chapter, we have discussed different features of metabolic engineering, including genetic manipulation of plants as well as microbes to increase production of taxol and its precursors.

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Abbreviations

10-DAB:

10-Deacetylbaccatin III

BAPT:

Baccatin III C-13-phenylpropanoyl-CoA transferase

BMS:

Bristol-Myers Squibb

DBAT:

10-Deacetylbaccatin III-10-O-acetyltransferase

DBTNBT:

3′-N-debenzoyl-2′-deoxytaxol N-benzoyl transferase

DMAPP:

Dimethylallyl pyrophosphate

FDA:

Food and Drug Administration

FDP:

Farnesyl diphosphate

GGPP:

Geranylgeranyl diphosphate

GGPPS:

Geranylgeranyl diphosphate synthase

IPI:

Isopentenyl diphosphate isomerase

IPP:

Isopentenyl pyrophosphate

MVA:

Mevalonic acid

NCI:

National Cancer Institute

PAM:

Phenylalanine aminomutase

T10βH:

Taxoid 10β-hydroxylase

TBT:

Taxane 2α-O-benzoyl transferase

TDAT:

Taxadiene-5α-ol-O-acetyltransferase

TXS:

Taxadiene synthase

USDA:

United States Department of Agriculture

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Acknowledgment

Subrata Kundu gratefully acknowledges to Council of Scientific and Industrial Research (CSIR), India, for providing Research Associate (RA) fellowship [Sanction No. 08/525(0004)/2014-EMR1].

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Authors and Affiliations

  1. Plant Biotechnology Laboratory, Department of Botany, Ramakrishna Mission Vivekananda Centenary College, Rahara, Kolkata, 700118, India

    Subrata Kundu & Biswajit Ghosh

  2. Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, India

    Sumita Jha

Authors
  1. Subrata Kundu
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  2. Sumita Jha
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  3. Biswajit Ghosh
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Correspondence to Biswajit Ghosh .

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Editors and Affiliations

  1. Department of Botany, Centre of Advanced Study, University of Calcutta, Kolkata, India

    Sumita Jha

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Kundu, S., Jha, S., Ghosh, B. (2017). Metabolic Engineering for Improving Production of Taxol. In: Jha, S. (eds) Transgenesis and Secondary Metabolism. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-28669-3_29

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