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Large-scale synthesis of globotriose derivatives through recombinant E. coli

机译:通过重组大肠杆菌大规模合成球三糖衍生物

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The carbohydrate chains decorating cell membranes and secreted proteins participate in a range of important biological processes. However, their ultimate significance and possible therapeutic potential have not been fully explored due to the lack of economical methods for their production. This study is an example of the use of a genetically engineered bacterial strain in the preparation of diverse oligosaccharides. Based on an ex vivo biosynthetic pathway, an artificial gene cluster was constructed by linking the genes of five associated enzymes on a plasmid vector. This plasmid was inserted into the E. coli NM522 strain to form globotriose-producing cells ('superbug' pLDR20-CKTUF). The specific strain was conveniently applied to the synthesis of globotriose trisaccharide and its derivatives, as potential neutralizers for Shiga toxin. This work demonstrates a novel and economical method for generating ligand diversity for carbohydrate drug development.
机译:装饰细胞膜的碳水化合物链和分泌的蛋白质参与了一系列重要的生物学过程。然而,由于缺乏生产它们的经济方法,它们的最终意义和可能的治疗潜力尚未得到充分探索。该研究是在多种寡糖制备中使用基因工程细菌菌株的实例。基于离体生物合成途径,通过将五个相关酶的基因连接到质粒载体上,构建了人工基因簇。将该质粒插入大肠杆菌NM522菌株中以形成产生球三糖的细胞(“ superbug” pLDR20-CKTUF)。该特定菌株可方便地应用于球果糖三糖及其衍生物的合成,作为志贺毒素的潜在中和剂。这项工作演示了一种新颖而经济的方法,可为碳水化合物药物开发产生配体多样性。

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