Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides
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 t...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56243-9 |
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| author | 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 Pengfei Tu |
| author_facet | 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 Pengfei Tu |
| author_sort | Wenqian Huang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1ac19ae06be948afa7a5f19427b1d4b6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1ac19ae06be948afa7a5f19427b1d4b62025-01-26T12:42:25ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56243-9Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosidesWenqian Huang0Yaru Yan1Weisheng Tian2Xiaoxue Cui3Yingxia Wang4Yuelin Song5Ting Mo6Xiping Xu7Saijing Zhao8Yuyu Liu9Xiaohui Wang10Juan Wang11Yong Jiang12Jun Li13She-po Shi14Xiao Liu15Pengfei Tu16Modern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversitySchool of Chinese Materia Medica, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese MedicineAbstract 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.https://doi.org/10.1038/s41467-025-56243-9 |
| spellingShingle | 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 Pengfei Tu Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides Nature Communications |
| title | Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides |
| title_full | Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides |
| title_fullStr | Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides |
| title_full_unstemmed | Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides |
| title_short | Complete pathway elucidation of echinacoside in Cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides |
| title_sort | complete pathway elucidation of echinacoside in cistanche tubulosa and de novo biosynthesis of phenylethanoid glycosides |
| url | https://doi.org/10.1038/s41467-025-56243-9 |
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