Abstract:
Glycosylation plays a pivotal role in tuning the folding and function of proteins. Because most human therapeutic proteins are glycosylated, understanding and controlling glycosylation is important for the design, optimization, and manufacture of biopharmaceuticals. Unfortunately, natural eukaryotic glycosylation pathways are complex and often produce heterogeneous glycan patterns, making the production of glycoproteins with chemically precise and homogeneous glycan structures difficult. To overcome these limitations, bacterial glycoengineering has emerged as a simple, cost-effective, and scalable approach to produce designer glycoprotein therapeutics and vaccines in which the glycan structures are engineered to reduce heterogeneity and improve biological and biophysical attributes of the protein. Here, we discuss recent advances in bacterial cell-based and cell-free glycoengineering that have enabled the production of biopharmaceutical glycoproteins with customized glycan structures.
摘要:
糖基化在调节蛋白质的折叠和功能中起关键作用。因为大多数人类治疗蛋白都是糖基化的,理解和控制糖基化对设计很重要,优化,和生物制药的制造。不幸的是,天然真核糖基化途径是复杂的,通常会产生异质聚糖模式,使得难以生产具有化学精确和均质聚糖结构的糖蛋白。为了克服这些限制,细菌糖工程已经成为一种简单的,成本效益高,和可扩展的方法来生产设计者糖蛋白治疗剂和疫苗,其中聚糖结构被设计为减少异质性并改善蛋白质的生物学和生物物理属性。这里,我们讨论了基于细菌细胞和无细胞的糖工程的最新进展,这些进展使得能够生产具有定制聚糖结构的生物制药糖蛋白。