The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla
Natural products from medicinal plants serve as an invaluable resource for drug discovery and development. However, low-abundance natural products are often understudied due to the challenges of obtaining sufficient quantities for pharmacological testing in cells or animals. Additionally, their comp...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2025-06-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X25000213 |
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| author | Yaran Suo Shuyu Li Haining Lyu Xin Zhao Jiale Xing Xin Chai Qian Zhang Chunjin Fu Chengchao Xu Jingjing Liao |
| author_facet | Yaran Suo Shuyu Li Haining Lyu Xin Zhao Jiale Xing Xin Chai Qian Zhang Chunjin Fu Chengchao Xu Jingjing Liao |
| author_sort | Yaran Suo |
| collection | DOAJ |
| description | Natural products from medicinal plants serve as an invaluable resource for drug discovery and development. However, low-abundance natural products are often understudied due to the challenges of obtaining sufficient quantities for pharmacological testing in cells or animals. Additionally, their complex stereochemistry and functional groups make chemical synthesis and purification difficult. In this study, we showcased the power of biosynthetic approaches to explore these underexplored compounds, using the low-abundance polyphyllin trillin 6′-O-glucoside from Paris polyphylla as an example. We identified two trillin 6′-O-glucosyltransferases required for its biosynthesis and successfully reconstructed the entire pathway in Nicotiana benthamiana. We demonstrated that trillin 6′-O-glucoside exhibits anti-bacterial activity comparable to major polyphyllins like polyphyllins I, II, and VII. Notably, it also showed much lower hemolytic activity, a common side effect of those major polyphyllins. Together, our study underscores the advantages of employing biosynthetic approaches to explore natural products that exist in low or trace abundances yet possess equally important pharmacological activities. |
| format | Article |
| id | doaj-art-34b26086d5534523b4d4948cff4b7dfa |
| institution | Kabale University |
| issn | 2405-805X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj-art-34b26086d5534523b4d4948cff4b7dfa2025-08-20T03:47:20ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-06-0110261061910.1016/j.synbio.2025.02.013The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphyllaYaran Suo0Shuyu Li1Haining Lyu2Xin Zhao3Jiale Xing4Xin Chai5Qian Zhang6Chunjin Fu7Chengchao Xu8Jingjing Liao9State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaCorresponding author.; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaCorresponding author; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaNatural products from medicinal plants serve as an invaluable resource for drug discovery and development. However, low-abundance natural products are often understudied due to the challenges of obtaining sufficient quantities for pharmacological testing in cells or animals. Additionally, their complex stereochemistry and functional groups make chemical synthesis and purification difficult. In this study, we showcased the power of biosynthetic approaches to explore these underexplored compounds, using the low-abundance polyphyllin trillin 6′-O-glucoside from Paris polyphylla as an example. We identified two trillin 6′-O-glucosyltransferases required for its biosynthesis and successfully reconstructed the entire pathway in Nicotiana benthamiana. We demonstrated that trillin 6′-O-glucoside exhibits anti-bacterial activity comparable to major polyphyllins like polyphyllins I, II, and VII. Notably, it also showed much lower hemolytic activity, a common side effect of those major polyphyllins. Together, our study underscores the advantages of employing biosynthetic approaches to explore natural products that exist in low or trace abundances yet possess equally important pharmacological activities.http://www.sciencedirect.com/science/article/pii/S2405805X25000213Paris polyphyllaTillin 6′-O-GlucosideAnti-bacterial activityHemolytic activityBiosynthesis |
| spellingShingle | Yaran Suo Shuyu Li Haining Lyu Xin Zhao Jiale Xing Xin Chai Qian Zhang Chunjin Fu Chengchao Xu Jingjing Liao The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla Synthetic and Systems Biotechnology Paris polyphylla Tillin 6′-O-Glucoside Anti-bacterial activity Hemolytic activity Biosynthesis |
| title | The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla |
| title_full | The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla |
| title_fullStr | The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla |
| title_full_unstemmed | The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla |
| title_short | The biosynthesis of trillin 6′-O-glucoside: A low-abundance yet pharmacologically active polyphyllin from Paris polyphylla |
| title_sort | biosynthesis of trillin 6 o glucoside a low abundance yet pharmacologically active polyphyllin from paris polyphylla |
| topic | Paris polyphylla Tillin 6′-O-Glucoside Anti-bacterial activity Hemolytic activity Biosynthesis |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X25000213 |
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