Characterization and protein engineering of glycosyltransferases for the biosynthesis of diverse hepatoprotective cycloartane-type saponins in Astragalus membranaceus
文献类型：期刊论文
| 作者 | Chen,Kuan; Zhang,Meng; Gao,Baihan; Hasan,Aobulikasimu; Li,Junhao; Bao,Yang'oujie; Fan,Jingjing; Yu,Rong; Yi,Yang; Agren,Hans |
| 刊名 | PLANT BIOTECHNOLOGY JOURNAL
 |
| 出版日期 | 2023 |
| 关键词 | astragalosides biosynthesis glycosyltransferases protein engineering Astragalus membranaceus FUNCTIONAL-CHARACTERIZATION UDP-GLYCOSYLTRANSFERASES CARBON-TETRACHLORIDE PROTOPANAXATRIOL PHARMACOLOGY GENERATION CHEMISTRY ACCURACY PATHWAY |
| ISSN号 | 1467-7652 |
| DOI | 10.1111/pbi.13983 |
| 英文摘要 | Although plant secondary metabolites are important source of new drugs, obtaining these compounds is challenging due to their high structural diversity and low abundance. The roots of Astragalus membranaceus are a popular herbal medicine worldwide. It contains a series of cycloartane-type saponins (astragalosides) as hepatoprotective and antivirus components. However, astragalosides exhibit complex sugar substitution patterns which hindered their purification and bioactivity investigation. In this work, glycosyltransferases (GT) from A. membranaceus were studied to synthesize structurally diverse astragalosides. Three new GTs, AmGT1/5 and AmGT9, were characterized as 3-O-glycosyltransferase and 25-O-glycosyltransferase of cycloastragenol respectively. AmGT1(G146V/I) variants were obtained as specific 3-O-xylosyltransferases by sequence alignment, molecular modelling and site-directed mutagenesis. A combinatorial synthesis system was established using AmGT1/5/9, AmGT1(G146V/S) and the reported AmGT8 and AmGT8(A394F). The system allowed the synthesis of 13 astragalosides in Astragalus root with conversion rates from 22.6% to 98.7%, covering most of the sugar-substitution patterns for astragalosides. In addition, AmGT1 exhibited remarkable sugar donor promiscuity to use 10 different donors, and was used to synthesize three novel astragalosides and ginsenosides. Glycosylation remarkably improved the hepatoprotective and SARS-CoV-2 inhibition activities for triterpenoids. This is one of the first attempts to produce a series of herbal constituents via combinatorial synthesis. The results provided new biocatalytic tools for saponin biosynthesis. |
| 学科主题 | Biotechnology & Applied Microbiology ; Plant Sciences |
| WOS记录号 | WOS:000908340600001 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/74912]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Chen,Kuan,Zhang,Meng,Gao,Baihan,et al. Characterization and protein engineering of glycosyltransferases for the biosynthesis of diverse hepatoprotective cycloartane-type saponins in Astragalus membranaceus[J]. PLANT BIOTECHNOLOGY JOURNAL,2023. |
| APA | Chen,Kuan.,Zhang,Meng.,Gao,Baihan.,Hasan,Aobulikasimu.,Li,Junhao.,...&Qiao,Xue.(2023).Characterization and protein engineering of glycosyltransferases for the biosynthesis of diverse hepatoprotective cycloartane-type saponins in Astragalus membranaceus.PLANT BIOTECHNOLOGY JOURNAL. |
| MLA | Chen,Kuan,et al."Characterization and protein engineering of glycosyltransferases for the biosynthesis of diverse hepatoprotective cycloartane-type saponins in Astragalus membranaceus".PLANT BIOTECHNOLOGY JOURNAL (2023). |
入库方式： OAI收割
来源：昆明植物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。