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.
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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Kundu, S., Jha, S., Ghosh, B. (2016). Metabolic Engineering for Improving Production of Taxol. In: Jha, S. (eds) Transgenesis and Secondary Metabolism. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-27490-4_29-1
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