Microbial factories for recombinant pharmaceuticals.

Microbial factories for recombinant pharmaceuticals.
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DOI:
10.1186/1475-2859-8-17
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发表时间:
2009-03-24
影响因子:
6.4
通讯作者:
Villaverde A
Villaverde A
中科院分区:
工程技术2区
文献类型:
--
作者:
Ferrer-Miralles N;Domingo-Espín J;Corchero JL;Vázquez E;Villaverde A

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迄今为止,美国食品药品监督管理局(FDA)和/或欧洲药品管理局(EMEA)批准用于人类使用的151种重组药物的生产宿主大多数是微生物细胞,无论是细菌还是酵母。这一事实表明,尽管微生物系统对有效生产功能性哺乳动物蛋白质造成了各种瓶颈和障碍,即缺乏或非常规的翻译后修饰、蛋白水解不稳定性、溶解性差和细胞应激反应的激活等,但它们代表了用于重组蛋白质生产的方便和强大的工具。在非微生物系统中生产的蛋白质药物数量的逐渐增加进入市场,并没有损害在微生物细胞中获得的产品的开发,证明了为蛋白质药物生产开发的细胞系统的微生物组(迄今为止为大肠杆菌和酿酒酵母)的稳健性。本文对这些药物的性质、性质、应用以及当前和潜在生产宿主的相关特征进行了比较。
Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative way.
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