Complete biosynthesis of the potent vaccine adjuvant QS-21
Complete biosynthesis of the potent vaccine adjuvant QS-21
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DOI：
10.1038/s41589-023-01538-5
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发表时间：
2024-01-26
影响因子：
14.8
通讯作者：
Osbourn，Anne
中科院分区：
文献类型：
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作者：
Martin，Laetitia B. B.;Kikuchi，Shingo;Osbourn，Anne
QS-21是一种有效的疫苗佐剂，目前从智利肥皂树中提取。它是带状疱疹，疟疾，2019冠状病毒病和其他正在开发的人类疫苗的关键组成部分。QS-21的结构由糖基化三萜支架与复杂的糖基化18-碳酰基链偶联组成，这对免疫刺激活性至关重要。我们先前确定了制造三萜糖苷支架所需的早期途径步骤;然而，刺激T细胞增殖所需的酰基链的生物合成途径是未知的。在这里，我们报告的酰基链的生物起源，其合成和添加所需的一系列酶的特征和重建烟草中的整个20步途径，从而证明了QS-21在异源表达系统中的生产。这一进展为疫苗佐剂的生物工程开辟了前所未有的机会，研究了结构-活性关系，并了解了这些化合物促进人类免疫反应的机制。
QS-21 is a potent vaccine adjuvant currently sourced by extraction from the Chilean soapbark tree. It is a key component of human vaccines for shingles, malaria, coronavirus disease 2019 and others under development. The structure of QS-21 consists of a glycosylated triterpene scaffold coupled to a complex glycosylated 18-carbon acyl chain that is critical for immunostimulant activity. We previously identified the early pathway steps needed to make the triterpene glycoside scaffold; however, the biosynthetic route to the acyl chain, which is needed for stimulation of T cell proliferation, was unknown. Here, we report the biogenic origin of the acyl chain, characterize the series of enzymes required for its synthesis and addition and reconstitute the entire 20-step pathway in tobacco, thereby demonstrating the production of QS-21 in a heterologous expression system. This advance opens up unprecedented opportunities for bioengineering of vaccine adjuvants, investigating structure–activity relationships and understanding the mechanisms by which these compounds promote the human immune response.