1Key Laboratory of Biomass Chemical Engineering of Ministry of Education, National Key Laboratory of Biobased Transportation Fuel Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China
2ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310000, China
3These authors contributed equally to this work
| Received 07 Mar 2024 |
Accepted 09 Apr 2024 |
Published 09 May 2024 |
Paclitaxel is a renowned broad-spectrum anticancer drug. With the establishment of a chromosome-level high-quality reference genome map of Taxus, recent research on paclitaxel biosynthesis has flourished. The oxetane ring is a distinctive chemical moiety of paclitaxel, and three recent studies have proposed different enzymes involved in its formation, reflecting divergent opinions on whether the pathway proceeds via acetylation followed by epoxidation or vice versa. Subsequently, researchers have elucidated gene clusters responsible for the biosynthesis of the key intermediate baccatin III. Despite varying reports, two studies successfully achieved heterologous biosynthesis of baccatin III by transient expression in tobacco. Taxadiene 5α-hydroxylase (T5αH), the first cytochrome P450 in the pathway, exhibited varied product profiles upon heterologous expression systems, contrasting with observations in native Taxus species, probably due to differences in partner proteins or cellular microenvironments. Further elucidation of biosynthesis mechanisms, including the reaction order and the promiscuity of key enzymes, is anticipated through collaborative efforts among botanists, chemists, and synthetic biologists.
