9IZ8

fungal unspecific peroxygenase from Thielavia terrestris

Summary for 9IZ8

• Entry DOI: 10.2210/pdb9iz8/pdb
• Descriptor: Heme haloperoxidase family profile domain-containing protein, PROTOPORPHYRIN IX CONTAINING FE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: fungal unspecific peroxygenase heme oxy-functionalization of carbon biosynthesis, biosynthetic protein
• Biological source: Thermothielavioides terrestris (strain ATCC 38088 / NRRL 8126) (Thielavia terrestris)
• Total number of polymer chains: 1
• Total formula weight: 25030.89

Authors

Lai, M.Y.,Yu, H.L. (deposition date: 2024-07-31, release date: 2025-12-24, Last modification date: 2025-12-31)

Primary citation

Lai, M.,Weng, Y.,Wei, J.,Lu, X.Y.,Huang, Z.,Li, H.,Huang, L.,Zhang, Z.,Zhu, L.,Xu, J.H.,Hong, R.,Yu, H.L.
Designing an oxidase toolbox for site-directed oxidation of taxanes.
Nat Commun, 2025

PubMed Abstract: Paclitaxel is one of the most prominent drugs for cancer therapy, and its synthesis has long been pursued by scientific community. Although the biosynthetic pathway has been gradually unraveled, its synthetic efficiency remains severely constrained by the low activity and low product selectivity of the hydrolases involved. In this study, an artificial toolbox of oxidases derived from mutants of TteUPO (unspecific peroxygenase from Thielavia terrestris) is developed for site-directed oxidation of taxanes at the C-4, C-6, C-10, C-11, C-12, and C-13 positions. Furthermore, de novo biosynthesis of oxidized taxadiene products is achieved in an engineered E. coli chassis. These findings offer an unconventional strategy for developing an efficient route toward paclitaxel and constructing paclitaxel analogs with different structures for medicinal evaluation.

PubMed: 41407708
DOI: 10.1038/s41467-025-67544-4

Experimental method

X-RAY DIFFRACTION (1.54 Å)