Synthetic Virus-like Particles for Glutathione Biosynthesis
Synthetic Virus-like Particles for Glutathione Biosynthesis
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用于谷氨酸生物合成的合成病毒样颗粒
DOI：
10.1021/acssynbio.0c00368
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发表时间：
2020-12-18
影响因子：
4.7
通讯作者：
Douglas, Trevor
中科院分区：
文献类型：
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作者：
Wang, Yang;Uchida, Masaki;Douglas, Trevor
自然界中发现的基于蛋白质的纳米区室激发了功能性纳米材料的开发，用于一系列应用，包括递送具有治疗效果的催化活性。由于谷胱甘肽（GSH）在代谢适应中起着至关重要的作用，许多疾病都与其缺乏有关，因此直接将GSH生物合成活性补充到疾病部位可能是一种潜在的治疗方法。在这里，我们报告了能够催化GSH生物合成的部分或完整途径的活性纳米反应器的成功设计和生产，这是通过将该途径的必需酶封装在来自噬菌体P22的病毒样颗粒（VLP）内来实现的。这些纳米反应器是专门为低聚生物分子的生物合成而设计的纳米笼的第一个例子。在纳米反应器的空腔内实现了酶的密集包装，这使我们能够在拥挤和受限的环境中研究酶的行为，包括酶动力学和蛋白质稳定性。此外，使用体外细胞培养模型证实了纳米反应器在保护免受氧化应激方面的生物医学效用。鉴于P22 VLP衣壳被认为是体内潜在的嗜肝纳米载体，因此将有希望测试这些GSH纳米反应器作为GSH缺乏性肝病的新治疗方法的功效。
Protein-based nanocompartments found in nature have inspired the development of functional nanomaterials for a range of applications including delivery of catalytic activities with therapeutic effects. As glutathione (GSH) plays a vital role in metabolic adaptation and many diseases are associated with its deficiency, supplementation of GSH biosynthetic activity might be a potential therapeutic when delivered directly to the disease site. Here, we report the successful design and production of active nanoreactors capable of catalyzing the partial or complete pathway for GSH biosynthesis, which was realized by encapsulating essential enzymes of the pathway inside the virus-like particle (VLP) derived from the bacteriophage P22. These nanoreactors are the first examples of nanocages specifically designed for the biosynthesis of oligomeric biomolecules. A dense packing of enzymes is achieved within the cavities of the nanoreactors, which allows us to study enzyme behavior, in a crowded and confined environment, including enzymatic kinetics and protein stability. In addition, the biomedical utility of the nanoreactors in protection against oxidative stress was confirmed using an in vitro cell culture model. Given that P22 VLP capsid was suggested as a potential liver-tropic nanocarrier in vivo, it will be promising to test the efficacy of these GSH nanoreactors as a novel treatment for GSH-deficient hepatic diseases.