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转基因绿色微藻的潜力;一种用于生产重组治疗性蛋白质的强大光生物反应器。

The potential of transgenic green microalgae; a robust photobioreactor to produce recombinant therapeutic proteins.

作者信息

Akbari Fariba, Eskandani Morteza, Khosroushahi Ahmad Yari

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

World J Microbiol Biotechnol. 2014 Nov;30(11):2783-96. doi: 10.1007/s11274-014-1714-0. Epub 2014 Aug 13.

Abstract

Microalgae have been used in food, cosmetic, and biofuel industries as a natural source of lipids, vitamins, pigments and antioxidants for a long time. Green microalgae, as potent photobioreactors, can be considered as an economical expression system to produce recombinant therapeutical proteins at large-scale due to low cost of production and scaling-up capitalization owning to the inexpensive medium requirement, fast growth rate, and the ease of manipulation. These microalgae possess all benefit eukaryotic expression systems including the ability of post-translational modifications required for proper folding and stability of active proteins. Among the many items regarded as recombinant protein production, this review compares the different expression systems with green microalgae like Dunaliella by viewing the nuclear/chloroplast transformation challenges/benefits, related selection markers/reporter genes, and crucial factors/strategies affecting the increase of foreign protein expression in microalgae transformants. Some important factors were discussed regarding the increase of protein yielding in microalgae transformants including: transformation-associated genotypic modifications, endogenous regulatory factors, promoters, codon optimization, enhancer elements, and milking of recombinant protein.

摘要

长期以来,微藻作为脂质、维生素、色素和抗氧化剂的天然来源,已被应用于食品、化妆品和生物燃料行业。绿藻作为高效的光生物反应器,由于生产成本低、扩大规模所需资金少(因其对培养基要求不高、生长速度快且易于操作),可被视为一种经济的大规模生产重组治疗性蛋白质的表达系统。这些微藻具备所有真核表达系统的优点,包括对活性蛋白质正确折叠和稳定性所需的翻译后修饰能力。在众多被视为重组蛋白生产的项目中,本综述通过审视核/叶绿体转化的挑战/益处、相关选择标记/报告基因以及影响微藻转化体中外源蛋白表达增加的关键因素/策略,将不同的表达系统与如杜氏盐藻等绿藻进行了比较。讨论了一些关于提高微藻转化体中蛋白质产量的重要因素,包括:与转化相关的基因型修饰、内源性调控因子、启动子、密码子优化、增强子元件以及重组蛋白的诱导表达。

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