Bioinformatic analysis and genetic engineering approaches for recombinant biopharmaceutical glycoproteins production in microalgae
Bioinformatic analysis and genetic engineering approaches for recombinant biopharmaceutical glycoproteins production in microalgae
复制标题
微藻重组生物制药糖蛋白生产的生物信息学分析和基因工程方法
DOI：
10.1016/j.algal.2021.102276
复制
发表时间：
2021-04-07
影响因子：
5.1
通讯作者：
Liang, Honghao
中科院分区：
文献类型：
--
作者：
Liu, Xiaojuan;Xi, Xihui;Liang, Honghao
近年来，利用微藻作为细胞工厂生产生物制药糖蛋白的兴趣显著增加。微藻通常通过蛋白质的翻译后修饰经由N-糖基化产生生物制药糖蛋白。生物制药糖蛋白的生物物理性质，如折叠，稳定性和分子识别受到N-糖基化过程的影响。因此，为了更好地了解生物制药糖蛋白的活性和功能，需要对微藻中N-糖基化的机制和途径进行全面的了解。在这项研究中，不同的微藻的全基因组数据库进行了评估的存在，以及假定的高尔基体糖基转移酶（GT）和糖苷酶（GS）的进化关系，使用全面的生物信息学技术。结果表明，GT、GS和成熟N-聚糖结构的存在和数量具有生物体特异性。由于GT和GS具有复杂的系统发育树和保守的基序结构，它们在不同生物中可能具有复杂的进化关系和多样的功能。微藻和人的N-糖基化途径高度不同，这表明必须做出许多努力来生产微藻中的人源化生物药用糖蛋白。因此，基因工程的方法，提出了五种不同的微藻改造的N-糖基化成人类兼容的N-聚糖。总之，微藻生物信息学分析和拟议的基因工程是未来生产具有人源化N-糖基化的功能性药物蛋白的必要条件。
In recent years, interest in the use of microalgae as cell factories to produce biopharmaceutical glycoproteins increased observably. Microalgae often produce biopharmaceutical glycoproteins through post-translational modification of proteins via N-glycosylation. The biophysical properties of biopharmaceutical glycoproteins such as folding, stability, and molecular recognition are influenced by the N-glycosylation process. Hence, to better understand the activity and function of biopharmaceutical glycoproteins there is a need for comprehensive knowledge on the mechanisms and pathways of N-glycosylation in microalgae. In this study, whole genome databases of different microalgae were assessed for the presence as well as the evolutionary relationship of putative Golgi glycosyltransferases (GTs) and glycosidases (GSs) using comprehensive bioinformatic techniques. The results showed that the presence and number of GTs, GSs, and mature N-glycan structures were organism specific. Since GTs and GSs had complex phylogenetic trees and conserved motif architectures, they potentially had complex evolutionary relationships and diverse functions in different organisms. Microalgal and human Nglycosylation pathways were highly distinct, and this indicated that many efforts must be made to produce humanized biopharmaceutical glycoproteins in microalgae. Hence, genetic engineering approaches were proposed for five different microalgae to remodel the N-glycosylation into human-compatible N-glycans. All in all, the bioinformatic analysis and the proposed genetic engineering in microalgae are essential for the future in producing functional pharmaceutical proteins with humanized N-glycosylation.