Synthetic Virus-like Particles for Glutathione Biosynthesis,ACS Synthetic Biology

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Synthetic Virus-like Particles for Glutathione Biosynthesis
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-11-24 , DOI: 10.1021/acssynbio.0c00368
Yang Wang ₁ , Masaki Uchida ₂ , Hitesh Kumar Waghwani ₁ , Trevor Douglas ₁

Affiliation

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.

中文翻译：

谷胱甘肽生物合成的合成病毒样颗粒

在自然界中发现的基于蛋白质的纳米隔室启发了功能纳米材料的开发，其用途广泛，包括传递具有治疗作用的催化活性。由于谷胱甘肽（GSH）在代谢适应中起着至关重要的作用，并且许多疾病都与它的缺乏有关，当直接将GSH生物合成活性传递到疾病部位时，其补充剂可能是一种潜在的治疗方法。在这里，我们报告成功设计和生产能够催化GSH生物合成的部分或完整途径的活性纳米反应器，这是通过将途径的必需酶封装在来源于噬菌体P22的病毒样颗粒（VLP）中实现的。这些纳米反应器是专门为寡聚生物分子的生物合成而设计的纳米笼的首例。在纳米反应器的腔体内实现了酶的密集包装，这使我们能够在拥挤而狭窄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，纳米反应器在抗氧化应激方面的生物医学效用已通过使用体外细胞培养模型。鉴于有人建议将P22 VLP衣壳作为体内潜在的嗜肝纳米载体，将有希望测试这些GSH纳米反应器作为治疗GSH缺乏型肝病的新方法的功效。

更新日期：2020-12-18

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