Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides

Wenqian Huang, Yaru Yan, Weisheng Tian, Xiaoxue Cui, Yingxia Wang, Yuelin Song, Ting Mo, Xiping Xu, Saijing Zhao, Yuyu Liu, Xiaohui Wang, Juan Wang, Yong Jiang, Jun Li (), She-po Shi (), Xiao Liu () and Pengfei Tu ()
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Wenqian Huang: Beijing University of Chinese Medicine
Yaru Yan: Beijing University of Chinese Medicine
Weisheng Tian: Beijing University of Chinese Medicine
Xiaoxue Cui: Beijing University of Chinese Medicine
Yingxia Wang: Beijing University of Chinese Medicine
Yuelin Song: Beijing University of Chinese Medicine
Ting Mo: Beijing University of Chinese Medicine
Xiping Xu: Beijing University of Chinese Medicine
Saijing Zhao: Beijing University of Chinese Medicine
Yuyu Liu: Beijing University of Chinese Medicine
Xiaohui Wang: Beijing University of Chinese Medicine
Juan Wang: Beijing University of Chinese Medicine
Yong Jiang: Peking University
Jun Li: Beijing University of Chinese Medicine
She-po Shi: Beijing University of Chinese Medicine
Xiao Liu: Beijing University of Chinese Medicine
Pengfei Tu: Beijing University of Chinese Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Echinacoside (ECH), one of the most representative phenylethanoid glycosides (PhGs), has considerable neuroprotective effects and is an effective ingredient in numerous commercial drugs. Here, we elucidate the complete ECH biosynthetic pathway in the medicinal plant Cistanche tubulosa. In total, 14 related genes are cloned and functionally characterized. Two upstream pathways for tyrosol biosynthesis from L-tyrosine are identified: one includes separate decarboxylation, deamination and reduction steps; the other uses microbial-like transamination, decarboxylation and reduction steps. In addition, a distinct downstream assembly process from tyrosol to ECH is revealed that includes sequential glucosylation, acylation, hydroxylation, and rhamnosylation to form acteoside, and ends with a final glucosylation converting acteoside to ECH. Furthermore, the de novo synthesis of 23 PhG derivatives is achieved via the heterologous expression of different combinations of the functional genes in tobacco. Our findings provide insights into the biosynthesis of ECH and a platform for alternative production of complex PhGs.

Date: 2025
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DOI: 10.1038/s41467-025-56243-9

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