Takaiwa Fumio, Wakasa Yuhya, Hayashi Shimpei, Kawakatsu Taiji
Plant Molecular Farming Unit, Division of Biotechnology, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Kannondai 2-1-2, Tsukuba, Ibaraki 305-8602, Japan.
Plant Molecular Farming Unit, Division of Biotechnology, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Kannondai 2-1-2, Tsukuba, Ibaraki 305-8602, Japan.
Plant Sci. 2017 Oct;263:201-209. doi: 10.1016/j.plantsci.2017.07.016. Epub 2017 Jul 28.
Cereal seed has been utilized as production platform for high-value biopharmaceutical proteins. Especially, protein bodies (PBs) in seeds are not only natural specialized storage organs of seed storage proteins (SSPs), but also suitable intracellular deposition compartment for recombinant proteins. When various recombinant proteins were produced as secretory proteins by attaching N terminal ER signal peptide and C terminal KDEL endoplasmic reticulum (ER) retention signal or as fusion proteins with SSPs, high amounts of recombinant proteins can be predominantly accumulated in the PBs. Recombinant proteins bioencapsulated in PBs exhibit high resistance to digestive enzymes in gastrointestinal tract than other intracellular compartments and are highly stable at ambient temperature, thus allowing oral administration of PBs containing recombinant proteins as oral drugs or functional nutrients in cost-effective minimum processed formulation. In this review, we would like to address key factors determining accumulation levels of recombinant proteins in PBs. Understanding of bottle neck parts and improvement of specific deposition to PBs result in much higher levels of production of high quality recombinant proteins.
谷物种子已被用作生产高价值生物制药蛋白的平台。特别是,种子中的蛋白体(PBs)不仅是种子贮藏蛋白(SSPs)的天然专门贮藏器官,也是重组蛋白合适的细胞内沉积区室。当通过连接N端内质网(ER)信号肽和C端KDEL内质网保留信号将各种重组蛋白作为分泌蛋白生产,或作为与SSPs的融合蛋白生产时,大量重组蛋白可主要积累在PBs中。与其他细胞内区室相比,生物封装在PBs中的重组蛋白对胃肠道中的消化酶具有更高的抗性,并且在环境温度下高度稳定,因此可以将含有重组蛋白的PBs作为口服药物或功能性营养物质以具有成本效益的最低加工制剂形式口服给药。在这篇综述中,我们将探讨决定重组蛋白在PBs中积累水平的关键因素。了解瓶颈部分并改善向PBs的特异性沉积可导致更高水平的高质量重组蛋白生产。