Unlocking saponin biosynthesis in soapwort

IF 12.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nature chemical biology Pub Date : 2024-07-23 DOI:10.1038/s41589-024-01681-7
Seohyun Jo, Amr El-Demerdash, Charlotte Owen, Vikas Srivastava, Dewei Wu, Shingo Kikuchi, James Reed, Hannah Hodgson, Alex Harkess, Shengqiang Shu, Chris Plott, Jerry Jenkins, Melissa Williams, Lori-Beth Boston, Elia Lacchini, Tongtong Qu, Alain Goossens, Jane Grimwood, Jeremy Schmutz, Jim Leebens-Mack, Anne Osbourn
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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.

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揭开肥皂草中皂甙生物合成的神秘面纱
皂草(Saponaria officinalis)是一种伞形科(Caryophyllaceae)开花植物,作为肥皂的传统来源已有悠久的历史。它之所以具有洗涤剂的特性,是因为它能产生极性化合物(皂苷),其中的主要成分是以齐墩果烷为基础的三萜类皂苷(皂苷 A 和 B)。皂草皂甙具有抗癌特性,也可作为肿瘤靶向治疗的内体逸出增强剂。有趣的是,这些皂苷与疫苗佐剂 QS-21 有着共同的结构特征,因此有可能成为皂苷佐剂前体的替代品。在这里,我们对 S. officinalis 的基因组进行了测序,并通过基因组挖掘和组合表达,鉴定出 14 种完成皂苷 B 生物合成途径的酶,其中包括添加 d-quinovose 所需的非典型胞质 GH1(糖苷水解酶家族 1)转糖苷酶。我们的研究结果为天然和新天然药物、给药剂和潜在的免疫刺激剂的获取和工程化开辟了道路。
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来源期刊
Nature chemical biology
Nature chemical biology 生物-生化与分子生物学
CiteScore
23.90
自引率
1.40%
发文量
238
审稿时长
12 months
期刊介绍: Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.
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