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. 2025 Jul;318(Pt 3):145152.
doi: 10.1016/j.ijbiomac.2025.145152. Epub 2025 Jun 11.

Multifunctional sesquiterpene synthase from Curcuma wenyujin reveals the biosynthetic mechanism of sesquiterpenes with diverse skeletons

Jing Ma  1 , Dengyu Li  1 , Mengdie Xu  1 , Yimeng Xia  1 , Gaowei Fang  1 , Qiuhui Wei  2 , Xiaoxia Ma  3 , Yifeng Zhang  4 , Qin Zhang  1 , Yuhan Hu  1 , Jiawei Zhou  5 , Xiaopu Yin  6 , Tianyuan Hu  7
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Multifunctional sesquiterpene synthase from Curcuma wenyujin reveals the biosynthetic mechanism of sesquiterpenes with diverse skeletons

Jing Ma et al. Int J Biol Macromol. 2025 Jul.

Abstract

Volatile sesquiterpenes derived from Curcuma wenyujin Y.H.Chen et C. Ling exhibit potent pharmacological activities but remain underexplored in terms of their biosynthesis. In this study, a multifunctional sesquiterpene synthase, CwTPS5, was identified from C. wenyujin, which can utilize farnesyl diphosphate (FPP) as a substrate to produce five distinct categories of sesquiterpenes based on their structural skeletons, resulting in at least 17 different sesquiterpene compounds, including previously unreported humulane-and spirane-type compounds in C. wenyujin. Many of its products serve as important active components or precursors of other bioactive sesquiterpenes found in volatile oils. Additionally, molecular docking-guided mutagenesis identified several key amino acids that regulate the product diversity of CwTPS5. Notably, the R456E and C404S mutations shifted product dominance from selinenes (81.4 %) to germacrene A (72.2 %) and hedycaryol (83.4 %), respectively. Overall, these findings provide valuable insights into the biosynthesis of sesquiterpenes in C. wenyujin and offer potential approaches for the production of these bioactive sesquiterpenes through metabolic engineering.

Keywords: Biosynthetic pathway; Catalytic mechanism; Curcuma wenyujin Y.H.Chen et C.Ling; Sesquiterpene; Sesquiterpene synthase.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

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