Systematic molecular dissection of key intermediates in xanthones biosynthesis in Cudrania tricuspidata and establishment of a viable heterologous expression system

被引:0
|
作者
Zhang, Jing [1 ]
Xu, Dan-Dan [1 ]
Zhu, Ting-Ting [1 ]
Ta, He [1 ]
Hao, Yue [1 ]
Zhang, Jiao-Zhen [1 ]
Fu, Jie [1 ]
Cheng, Ai-Xia [1 ]
Lou, Hong-Xiang [1 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Benzophenone 3 ' -hydroxylase; benzophenone synthase; Benzoyl-coenzyme A ligase; Cudrania tricuspidata; Heterogenous biosynthesis; Xanthone derivatives; BENZOPHENONE SYNTHASE; CHALCONE SYNTHASE; NATURAL-PRODUCTS; CELL-CULTURES; COENZYME; BENZOATE; LIGASE; PURIFICATION; INSIGHTS;
D O I
10.1016/j.plaphy.2025.109524
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
The major phytochemicals in the roots of Cudrania tricuspidata are prenylated xanthones, exhibiting significant structural diversity and bioactive properties, such as anti-inflammatory, antioxidative, and antitumor effects. The biosynthetic pathways of these compounds have not yet been resolved, limiting their production through synthetic biology. In this study, benzoyl-coenzyme A (CoA) ligase (BZL), benzophenone synthase (BPS), and benzophenone 3 '-hydroxylase (B3 ' H) transcripts involved in the biosynthesis of xanthone were cloned and characterized from C. tricuspidata. The results showed that C. tricuspidata BZL (CtBZL) catalyzed the formation of benzoyl-CoA from benzoate and C. tricuspidata BPS (CtBPS) catalyzed the condensation of benzoyl-CoA and three molecules of malonyl-CoA to form 2,4,6-trihydroxybenzophenone (2,4,6-triHB) via Claisen type cyclization. Then, C. tricuspidata B3 ' H (CtB3 ' H) hydroxylated 2,4,6-triHB to produce 2,3 ',4,6-tetrahydroxybenzophenone (2,3 ',4,6-tetraHB), which was a key precursor of xanthone derivatives. In addition, the functions of the enzymes were further explored by the heterologous expression of CtBZL, CtBPS, and CtB3 ' H in Saccharomyces cerevisiae and Nicotiana benthamiana. Also, a preliminary heterologous synthesis system of 2,3 ',4,6-tetraHB was established. The present study provided the candidate genes and strategies for the heterologous production of xanthones using S. cerevisiae and N. benthamiana as hosts.
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页数:10
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