Abstract
Paclitaxel is a tricyclic diterpenoid first isolated from the bark of Taxus brevifolia. It is notably one of the most effective natural anticancer drugs discovered so far, and has been widely used in the treatment of breast, ovarian, lung cancer, as well as other diseases. However, the content of paclitaxel in the bark of yew trees is extremely low, thus alternative sources need to be developed urgently to meet the clinical demands. Using methods of synthetic biology to realize the heterologous expression of paclitaxel-related genes in microbial hosts could be a good choice. This paper reviews the advances in the researches on the biosynthesis of paclitaxel to provide new research strategies and insights.
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Abbreviations
- IPP:
-
Isopentenyl diphosphate
- DMAPP :
-
Dimethylallyl diphosphate
- MVA:
-
Mevalonate
- MEP:
-
2-C-methyl-D-erythritol 4-phosphate
- GGPP:
-
Geranylgeranyl diphosphate
- GGPPS:
-
Geranylgeranyl diphosphate synthase
- NSCLC:
-
Non-small cell lung cancer
- MSA:
-
Microtubules-stabilizing agent
- ABC:
-
ATP-binding cassette
- TXS:
-
Taxadiene synthase
- T5alphaH:
-
Taxadiene-5alpha-hydroxylase
- TAT:
-
Taxadien-5alpha-ol-O-acetyltransferase
- T10betaH:
-
Taxane 10beta-hydroxylase
- T13alphaH:
-
Taxane 13alpha-hydroxylase
- T14betaH:
-
Taxane 14beta-hydroxylase
- TBT:
-
Taxane 2alpha -O-benzoyl transferase
- DBAT:
-
10-deacetylbaccatin III 10-O-acetyltransferase
- PAM:
-
Phenylalanine aminomutase
- 4CL:
-
4-coumarate-CoA ligases
- BAPT:
-
Baccatin III amino phenylpropanoyl-13-O-transferase
- DBTNBT:
-
Taxane N-debenzoyltransferase
- MMME:
-
Multivariate modular metabolic engineering
- OCT:
-
5(12)-oxa-3(11)-cyclotaxane
- iso-OCT:
-
5(11)-oxa-3(11)-cyclotaxane
- XDT:
-
7-xylosyl-10-deacetylbaccatin
- DT:
-
10-deacetyltaxol
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This work was supported by the National Key R&D Program of China (2020YFA0908000), the National Natural Science Foundation of China (81773830 & 82003894), the Key Project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources (2060302-1806-03), and National Program for Special Support of Eminent Professionals.
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Y. F. L. and Y. T. wrote the manuscript. Y. T. and W. G. provided guidance. All authors read and approved the final manuscript.
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Tong, Y., Luo, Y.F. & Gao, W. Biosynthesis of paclitaxel using synthetic biology. Phytochem Rev 21, 863–877 (2022). https://doi.org/10.1007/s11101-021-09766-0
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DOI: https://doi.org/10.1007/s11101-021-09766-0