Total biosynthesis of the medicinal triterpenoid saponin astragalosides

IF 15.8 1区 生物学 Q1 PLANT SCIENCES
Bingyan Xu, Jian-Ping Huang, Guoqing Peng, Wenying Cao, Zhong Liu, Yin Chen, Jingchun Yao, Yong-Jiang Wang, Jie Li, Guimin Zhang, Shilin Chen, Sheng-Xiong Huang
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引用次数: 0

Abstract

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. Astragaloside IV, the key active compound in Radix Astragali, a medicinal plant used for immunomodulation in Asia and Europe, now has a fully elucidated biosynthetic pathway, enabling its efficient production through synthetic biology.

Abstract Image

Abstract Image

药用三萜皂甙黄芪皂甙的总生物合成
黄芪被用于传统中药已有 2000 多年的历史。其主要活性三萜类皂甙--黄芪皂甙因具有多种保健功效和医学应用而备受关注。尽管如此,黄芪皂苷的生物合成机制仍然是个谜。在这里,我们生成了膜荚果的染色体级基因组。通过鉴定黄芪皂苷生物合成所需的两种定制酶,发现了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。该途径的特点是一系列选择性羟化、环氧化和糖基化反应,这些反应由三个细胞色素 P450、一个依赖于 2-氧代戊二酸的二氧化酶和两个糖基转移酶介导。在烟曲霉中重建这种生物合成机制可以异源生产黄芪皂苷 IV。这些发现为解决与黄芪苷相关的来源问题奠定了坚实的基础,并拓宽了我们对萜烯生物合成基因簇多样性的认识。
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来源期刊
Nature Plants
Nature Plants PLANT SCIENCES-
CiteScore
25.30
自引率
2.20%
发文量
196
期刊介绍: Nature Plants is an online-only, monthly journal publishing the best research on plants — from their evolution, development, metabolism and environmental interactions to their societal significance.
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