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Discovering and harnessing oxidative enzymes for chemoenzymatic synthesis and diversification of anticancer camptothecin analogues
ChemistryCommunications 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.... show more
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Abstract
Semi-synthetic derivatives of camptothecin (CPT), a quinoline alkaloid from Camptotheca acuminata, are potent anticancer agents. Here, two C. acuminata cytochrome P450 monooxygenases were discovered that catalyze regio-specific 10- and 11-oxidations of CPT. Using these enzymes, combinatorial chemoenzymatic C–H functionalizations of the CPT scaffold produced a suite of anticancer drugs, including topotecan (Hycamtin) and irinotecan (Camptosar). This work elucidates camptothecin metabolism and provides greener approaches to access clinically relevant CPT 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
DOI
https://doi.org/10.1038/s42004-021-00602-2
Tags
cytochrome P450camptothecinanticancer drugsoxidationcombinatorial chemoenzymatic
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