β-Terrecyclene synthase constructs the quadrane backbone in terrecyclic acid biosynthesis

Yongxiang Song; Wengui Wang; Jiafan Yang; Dewei Gao; John M. Billingsley; Songtao Wang; Yiguang Zhu; Junfeng Wang; Jianhua Ju; Yan Yan; Yi Tang

doi:10.1039/D4SC01208A

β-Terrecyclene synthase constructs the quadrane backbone in terrecyclic acid biosynthesis†

Yongxiang Song,^abcd Wengui Wang,

^f Jiafan Yang,^abc Dewei Gao,

^d John M. Billingsley,^d Songtao Wang,^abc Yiguang Zhu,^abcd Junfeng Wang,

^abcd Jianhua Ju,

^ac Yan Yan

*^abcd and Yi Tang

^de

Author affiliations

* Corresponding authors

^a Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China
E-mail: yyan@scsio.ac.cn

^b Sanya Institute of Oceanology Eco-Environmental Engineering Yazhou Scientific Bay, Sanya, China

^c University of Chinese Academy of Science, 19 Yuquan Road, Beijing 100049, China

^d Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA

^e Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA

^f School of Chemistry and Chemical Engineering, University of Jinan, 336 West Road of Nan Xinzhuang, Jinan 250022, China

Abstract

Quadrane sesquiterpenes featuring a distinctive tricyclic skeleton exhibit potent antimicrobial and anticancer activities. Although extensive studies have attempted to reveal the multistep carbocation rearrangement involved in the formation of the tricyclic quadrane scaffold, the exact biosynthetic pathway and chemical logic to generate the quadrane structure remains mysterious. Here we identified a novel sesquiterpene synthase that is capable of generating β-terrecyclene possessing the quadrane scaffold and characterized the biosynthetic pathway of a representative fungal quadrane terrecyclic acid. Further mutagenesis coupled with isotopically sensitive branching studies of this β-terrecyclene synthase provided insight into the mechanism involved in the formation of the quadrane scaffold.

This article is part of the themed collections: 2024 Chemical Science HOT Article Collection and 2024 ChemSci Pick of the Week Collection

Chemical Science

β-Terrecyclene synthase constructs the quadrane backbone in terrecyclic acid biosynthesis†

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β-Terrecyclene synthase constructs the quadrane backbone in terrecyclic acid biosynthesis

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