Key Laboratory of Phytochemistry and Natural Medicines and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
University of the Chinese Academy of Sciences, Beijing, China.
Nat Plants. 2024 Nov;10(11):1826-1837. doi: 10.1038/s41477-024-01827-4. Epub 2024 Oct 21.
Astragalus membranaceus has been used in traditional Chinese medicine for over 2,000 years. Its major active triterpenoid saponins, astragalosides, have attracted great attention due to their multiple health benefits and applications in medicine. Despite this, the biosynthetic machinery for astragalosides remains enigmatic. Here a chromosome-level genome assembly of A. membranaceus was generated. The identification of two tailoring enzymes required for astragaloside biosynthesis enabled the discovery of a triterpenoid biosynthetic gene cluster, leading to elucidation of the complete astragaloside biosynthetic pathway. This pathway is characterized by a sequence of selective hydroxylation, epoxidation and glycosylation reactions, which are mediated by three cytochrome P450s, one 2-oxoglutarate-dependent dioxygenase and two glycosyltransferases. Reconstitution of this biosynthetic machinery in Nicotiana benthamiana allowed for heterologous production of astragaloside IV. These findings build a solid foundation for addressing the sourcing issues associated with astragalosides and broaden our understanding of the diversity of terpene biosynthetic gene clusters.
黄芪在中医药中已经使用了 2000 多年。其主要的活性三萜皂苷类化合物黄芪甲苷由于具有多种健康益处，并且在医学上有多种应用而备受关注。尽管如此，黄芪皂苷的生物合成机制仍然是个谜。本研究对黄芪进行了染色体水平的基因组组装。鉴定出了两个催化黄芪皂苷生物合成的修饰酶，发现了一个三萜类生物合成基因簇，从而阐明了完整的黄芪皂苷生物合成途径。该途径的特征是一系列选择性的羟化、环氧化和糖基化反应，由三个细胞色素 P450、一个 2-氧戊二酸依赖性双加氧酶和两个糖基转移酶介导。在本氏烟中重建该生物合成机制，实现了黄芪甲苷 IV 的异源生产。这些发现为解决黄芪甲苷的来源问题奠定了坚实的基础，并拓宽了我们对萜类生物合成基因簇多样性的认识。
