Citation: Shao-Yang Li, Jia-Cheng Huang, Ya-Lin Wang, Hong-Ting Zhen, Yu Fan, Zheng-Qun Zhou, Guo-Dong Chen, Jian-Ming Lv, Gao-Qian Wang, Dan Hu, Hao Gao. Structural and catalytic mechanisms of two N-hydroxycinnamoyltransferases underlying lycibarbarspermidines biosynthesis in wolfberry[J]. Chinese Chemical Letters, ;2026, 37(9): 112813. doi: 10.1016/j.cclet.2026.112813 shu

Structural and catalytic mechanisms of two N-hydroxycinnamoyltransferases underlying lycibarbarspermidines biosynthesis in wolfberry

Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China

tghao@jnu.edu.cn

thudan@jnu.edu.cn

gqwang@jnu.edu.cn

Received Date: 21 January 2026
Revised Date: 18 April 2026
Accepted Date: 20 April 2026
Available Online: 22 April 2026

Figures(5)

Lycibarbarspermidines represent a major class of bioactive components in wolfberry (the fruit of Lycium barbarum), consisting of di-phenylpropionyl spermidines and their glucosides. While the molecular basis underlying their glycodiversity was clarified in our previous work, the biosynthesis of di-phenylpropionyl spermidine core structure remains elusive. In particular, the acyltransferase responsible for conjugating dihydrocaffeoyl, one of the dominant phenylpropionyl moieties, is still unidentified. Herein, two N-hydroxycinnamoyltransferases (LbSCT1/2) from wolfberry were identified, which not only catalyze the conjugation of spermidine with caffeoyl-CoA, but also exhibit high catalytic activity toward dihydrocaffeoyl-CoA. Notably, LbSCT2 catalyzes monoacylation, whereas LbSCT1 enables sequential diacylation. Together with caffeoyl-CoA double bond reductase (LbDBR2), LbSCT1/2 accomplish the biosynthesis of lycibarbarspermidine Ⅰ-Ⅳ. Furthermore, LbSCT1 efficiently catalyzes the biosynthesis of kukoamine B, a major bioactive component from Lycii Cortex (the root bark of Lycium species). Crystal structural and mutagenic investigations elucidated the catalytic mechanisms underlying the selectivity of LbSCT1/2 for spermidine mono- and diacylation. This study establishes the complete biosynthesis of lycibarbarspermidines and provides valuable enzymatic tools for diversifying phenylpropionyl compounds.
- Wolfberry,
- Lycibarbarspermidines,
- Biosynthesis,
- N-Hydroxycinnamoyltransferases,
- Crystal structure,
- Catalytic mechanism
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