Citation: Ke Gao, Lin Zhao, Lei Wang, Rui Zhang, Jianxun Zhu, Pengcheng Lin, Jiachen Zi. Mining substrate-promiscuity cytochrome P450s from Euphorbia fischeriana for heterologous bioproduction of diverse labdane-related diterpenoids[J]. Chinese Chemical Letters, ;2026, 37(1): 110903. doi: 10.1016/j.cclet.2025.110903 shu

Mining substrate-promiscuity cytochrome P450s from Euphorbia fischeriana for heterologous bioproduction of diverse labdane-related diterpenoids

Ke Gao ^{a, 1} ,
Lin Zhao ^{a, 1} ,
Lei Wang ^a ,
Rui Zhang ^a ,
Jianxun Zhu ^{a, *,} ,
Pengcheng Lin ^{b, *,} ,
Jiachen Zi ^{a, *,}

a.
State 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 and Peking Union Medical College, Beijing 100050, China
b.
Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai University for Nationalities, Xining 810007, China

zhujianxun@imm.ac.cn

qhlpc@126.com

zijiachen@imm.ac.cn

Received Date: 17 December 2024
Revised Date: 22 January 2025
Accepted Date: 26 January 2025
Available Online: 31 January 2025

Figures(3)

Many labdane-related diterpenoids (LRDs) exhibit high values in drug development. Their diversity in structure and bioactivity, to a large extent, arise from oxidative modifications which are mainly catalyzed by cytochrome P450s (CYPs). The medicinal plant Euphorbia fischeriana Steud. is rich in LRDs with distinct scaffolds. Herein, we characterized three cytochrome P450s involved in LRD biosynthesis from this plant. Notably, CYP71D450 and CYP701A148 are two substrate-promiscuity CYPs. The former is the first example of CYPs which can oxidize C-3 of ent–atisane skeleton and ent–isopimara-7(8),15-diene, and the latter is the first example of CYPs which can oxidize C-19 of ent–abietane and ent–pimarane skeletons. This study expands the toolkit for bioproduction of diverse LRDs.
- Labdane-related diterpenoids,
- Biosynthesis,
- Cytochrome P450,
- Bioproduction,
- Euphorbia fischeriana
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