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解析肥皂草中皂苷生物合成的奥秘。

Unlocking saponin biosynthesis in soapwort.

作者信息

Jo Seohyun, El-Demerdash Amr, Owen Charlotte, Srivastava Vikas, Wu Dewei, Kikuchi Shingo, Reed James, Hodgson Hannah, Harkess Alex, Shu Shengqiang, Plott Chris, Jenkins Jerry, Williams Melissa, Boston Lori-Beth, Lacchini Elia, Qu Tongtong, Goossens Alain, Grimwood Jane, Schmutz Jeremy, Leebens-Mack Jim, Osbourn Anne

机构信息

Department of Biochemistry and Metabolism, John Innes Centre, Norwich Research Park, Norwich, UK.

Department of Chemistry, Faculty of Sciences, Mansoura University, Mansoura, Egypt.

出版信息

Nat Chem Biol. 2025 Feb;21(2):215-226. doi: 10.1038/s41589-024-01681-7. Epub 2024 Jul 23.

Abstract

Soapwort (Saponaria officinalis) is a flowering plant from the Caryophyllaceae family with a long history of human use as a traditional source of soap. Its detergent properties are because of the production of polar compounds (saponins), of which the oleanane-based triterpenoid saponins, saponariosides A and B, are the major components. Soapwort saponins have anticancer properties and are also of interest as endosomal escape enhancers for targeted tumor therapies. Intriguingly, these saponins share common structural features with the vaccine adjuvant QS-21 and, thus, represent a potential alternative supply of saponin adjuvant precursors. Here, we sequence the S. officinalis genome and, through genome mining and combinatorial expression, identify 14 enzymes that complete the biosynthetic pathway to saponarioside B. These enzymes include a noncanonical cytosolic GH1 (glycoside hydrolase family 1) transglycosidase required for the addition of D-quinovose. Our results open avenues for accessing and engineering natural and new-to-nature pharmaceuticals, drug delivery agents and potential immunostimulants.

摘要

肥皂草(肥皂草)是石竹科的一种开花植物,长期以来一直被人类用作传统的肥皂来源。其去污特性归因于极性化合物(皂苷)的产生,其中基于齐墩果烷的三萜皂苷——肥皂草皂苷A和B是主要成分。肥皂草皂苷具有抗癌特性,作为靶向肿瘤治疗的内体逃逸增强剂也备受关注。有趣的是,这些皂苷与疫苗佐剂QS-21具有共同的结构特征,因此代表了皂苷佐剂前体的潜在替代来源。在这里,我们对肥皂草基因组进行了测序,并通过基因组挖掘和组合表达,鉴定出14种完成通往肥皂草皂苷B生物合成途径的酶。这些酶包括添加D-奎诺糖所需的非典型胞质GH1(糖苷水解酶家族1)转糖苷酶。我们的研究结果为获取和改造天然及新型药物、药物递送剂和潜在免疫刺激剂开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6b/11782082/c9b9b65a1a46/41589_2024_1681_Fig1_HTML.jpg

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