Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III
Agricultural Genomics Institute at Shenzhen · Chinese Academy of Agricultural Sciences · +8 more institutions
Abstract
Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible…
Citation impact
- FWCI
- 73.17
- Percentile
- 100%
- References
- 80
Authors
24- BJBin JiangCorresponding
Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs
- LGLei GaoCorresponding
Beijing National Laboratory for Molecular Sciences
- HWHaijun WangCorresponding
Agricultural Genomics Institute at Shenzhen, Beijing National Laboratory for Molecular Sciences, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs
- HWHaijun Wang
South China Agricultural University, Agricultural Genomics Institute at Shenzhen, Beijing National Laboratory for Molecular Sciences, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs
- YSYa‐Ping SunCorresponding
South China Agricultural University, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs
Topics & keywords
- Taxus
- Biosynthesis
- Chemistry
- Stereochemistry
- Enzyme
- Taxane
- Oxetane
- Biochemistry
- Good health and well-being