From pathway discovery to microbial factories: Taxol and bilobalide

PhD defence by Yuman Xie

Assessment Committee

Associate Professor Tomas Laursen, Department of Plant and Environmental Sciences, University of Copenhagen (Chairperson)
Researcher Grade A (Research Professor) Antonios Makris, Centre of Research and Technology Hellas
Senior Researcher Carlos G. Acevedo-Rocha, DTU

Supervisors

Professor Sotirios Kampranis
Assistant Professor Feiyan Liang
Assistant Professor Irini Pateraki

Department

Department of Plant and Environmental Sciences

Place

The defence is conducted as a hybrid defence.

To attend the defence in person:
Room: aud - A2-70.03, Thorvaldsensvej 40, 1871, Frederiksberg

To attend the defence online:
Please follow the link to attend the defence online: https://ucph-ku.zoom.us/j/63628987443?pwd=O5j9BpkiLbb0OU2WZkRox9ldHEjx3W.1

Email address to gain access to the thesis: yuman@plen.ku.dk.
You will either receive a copy of the thesis or be informed where you can read a physical copy.
Recipients of copies of the thesis are not allowed to share or distribute it due to copyright compliance.

Short description of the thesis

This thesis explores the biosynthesis and microbial production of two high-value plant terpenoids: Taxol from Taxus species and bilobalide from Ginkgo biloba. Taxol is a clinically important anticancer drug, while bilobalide is a bioactive sesquiterpene with potential neuroprotective, anti-inflammatory, and cardiovascular benefits. For Taxol, the two final missing enzymes, T2′OGD and T3′NBT, were identified, completing the biosynthetic pathway from baccatin III to Taxol. The pathway was reconstructed in Nicotiana benthamiana, Saccharomyces cerevisiae, and Escherichia coli, with metabolic engineering increasing Taxol production in E. coli to 15 mg/L. For bilobalide, an active sesquiterpene synthase was identified and co-expressed with three cytochrome P450 enzymes, providing a foundation for further elucidation of its biosynthesis.