Citation: Kunya Wang, Bingyu Liu, Daojiang Yan, Jian Bai, Haibo Yu, Youcai Hu. Full biosynthetic pathway of pyrrolobenzoxazines[J]. Chinese Chemical Letters, ;2025, 36(1): 109811. doi: 10.1016/j.cclet.2024.109811 shu

Full biosynthetic pathway of pyrrolobenzoxazines

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

huyoucai@imm.ac.cn

Received Date: 14 February 2024
Revised Date: 18 March 2024
Accepted Date: 21 March 2024
Available Online: 22 March 2024

Figures(4)

Pyrrolobenzoxazines are a rare terpene-amino acid family of natural products with potent biological activities. Here, we reported the full biosynthetic pathway of paeciloxazine (1), a typical pyrrolobenzoxazine, with significant insecticidal activity. Base on heterologous expression, chemical complement experiment, and in vitro biochemical assays, we demonstrated the sesquiterpene portion of 1 derived from discontinuously oxidations of amorphdiene, in which P450 monooxygenase PaxH catalyzed a cascade of hydroxylation and epoxidation, while two flavin dependent monooxygenases are involved in the transformation of the esterified tryptophan into a pyrrolobenzoxazine core. Furthermore, a total of 15 compounds were generated through heterologous expression, of which 13, 17 and 20 showed potential antiepileptic activity. This study fully elucidated the biosynthetic pathway of paeciloxazine (1) and showed the diversity and complexity of constructing natural products by organisms.
- Pyrrolobenzoxazines,
- Paeciloxazine,
- Biosynthesis,
- P450 monooxygenase,
- Antiepileptic activity
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