Chemistry

Discovering and harnessing oxidative enzymes for chemoenzymatic synthesis and diversification of anticancer camptothecin analogues

T. M. Nguyen, T. Nguyen, et al.

This groundbreaking research unveils two cytochrome P450 monooxygenases from *Camptotheca acuminata* that specifically oxidize camptothecin, paving the way for innovative anticancer drug production, including topotecan and irinotecan. Authored by Tuan-Anh M. Nguyen, Trinh-Don Nguyen, Yuen Yee Leung, Matthew McConnachie, Oleg Sannikov, Zhicheng Xia, and Thu-Thuy T. Dang, the study highlights environmentally friendly methods for synthesizing important medicinal derivatives.

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Abstract

This research discovered two cytochrome P450 monooxygenases from *Camptotheca acuminata* that catalyze the regio-specific oxidation of camptothecin. These enzymes were used in combinatorial chemoenzymatic C-H functionalizations to produce various anticancer drugs, including topotecan and irinotecan. This work provides insights into camptothecin metabolism and offers greener approaches for producing clinically relevant derivatives.

Publisher

Communications Chemistry

Published On

Dec 16, 2021

Authors

Tuan-Anh M. Nguyen, Trinh-Don Nguyen, Yuen Yee Leung, Matthew McConnachie, Oleg Sannikov, Zhicheng Xia, Thu-Thuy T. Dang

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