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Published on: March 7, 2025
Mining Cytochrome P450 Enzymes Involved in Casbene Oxidation from Euphorbia fischeriana Steud. and Clarifying Their
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, and NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing100050, China.
Abstract:
Casbanes and the related diterpenoids (e.g., lathyranes, tiglianes, and ingenanes) are yielded from oxidation and oxidation-mediated cyclization of casbene, in which cytochrome P450 enzymes (CYPs) play vital roles. Herein, we characterized four CYPs involved in casbene oxidation from Euphorbia fischeriana Staud. The discovery of these CYPs enables oxidation of C-16, C-17, and C-19 of casbene, which has not been achieved by the previously characterized CYPs. And we found that casbene-5-oxidases can catalyze both 5S- and 5R-hydroxylation of casbene, but not only 5S-hydroxylation as previously reported. Moreover, the CYP orthologues (e.g., casbene-5,6-oxidases EfCYP726A47 and ElCYP726A27) involved in casbene oxidation in Euphorbiaceae may possess different substrate specificity. Overall, this study expands the enzymatic tools for casbene oxidation and exhibits the complexity of casbene-related diterpenoid biosynthesis.
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