Nature Chemical Biology ( IF 12.9 ) Pub Date : 2024-07-23 , DOI: 10.1038/s41589-024-01681-7 Seohyun Jo 1 , Amr El-Demerdash 1, 2 , Charlotte Owen 1 , Vikas Srivastava 1, 3 , Dewei Wu 1 , Shingo Kikuchi 1 , James Reed 1 , Hannah Hodgson 1 , Alex Harkess 4 , Shengqiang Shu 5 , Chris Plott 4 , Jerry Jenkins 4 , Melissa Williams 4 , Lori-Beth Boston 4 , Elia Lacchini 6, 7 , Tongtong Qu 6, 7 , Alain Goossens 6, 7 , Jane Grimwood 4 , Jeremy Schmutz 4, 5 , Jim Leebens-Mack 8 , Anne Osbourn 1
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.
中文翻译:
解锁肥皂草中的皂苷生物合成
肥皂草 ( Saponaria officinalis ) 是石竹科的一种开花植物,作为传统的肥皂来源,人类使用它已有悠久的历史。其洗涤特性是由于产生了极性化合物(皂苷),其中齐墩果烷类三萜皂苷、皂苷 A 和 B 是主要成分。皂草皂苷具有抗癌特性,并且作为靶向肿瘤治疗的内体逃逸增强剂也令人感兴趣。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供应。在这里,我们对S进行排序。药用植物基因组,并通过基因组挖掘和组合表达,鉴定出完成皂苷 B 生物合成途径的 14 种酶。这些酶包括添加d-奎诺糖所需的非经典胞质 GH1(糖苷水解酶家族 1)转糖苷酶。我们的研究结果为获取和设计天然和新天然药物、药物输送剂和潜在的免疫刺激剂开辟了途径。