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糖基工程指导了基于UPEC O21 O-抗原多糖的糖蛋白新生生物制造
Yuhui Wang1, Andrei V Perepelov2, Sof'ya N Senchenkova2
1Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin, China; TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin, China; National Glycoengineering Research Center, Shandong University, Qingdao, Shandong 266237, China.
工程细菌生产O21 O-抗原多糖类糖蛋白,一种潜在的疫苗,对Uropathogenic Escherichia coli (UPEC) O21感染. 这种新型的糖基平台显著提高了产量,并在体内表现出免疫反应.
科学领域:
- 生物技术是生物技术.
- 疫苗开发 疫苗开发
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 糖蛋白是重要的治疗生物分子.
- 泌尿病原性大肠杆菌 (UPEC) O21在全球范围内导致尿路感染的增加.
- 迫切需要有效的UPEC O21疫苗.
研究的目的:
- 设计一种非致病性大肠杆菌菌株,以实现O21 O-抗原多糖基糖蛋白的经济有效生物合成.
- 开发一种潜在的针对UPEC O21感染的候选疫苗.
主要方法:
- 工程E. coli MG1655用于葡萄糖-甘油的共同利用和O-糖化.
- 增强了UDP-糖前体路径,以增加碳流量.
- 为糖蛋白生产优化培养条件.
主要成果:
- 在糖蛋白标位上实现了5.6倍的增强.
- 产生的高达35.34毫克/升的糖蛋白.
- 通过糖MS确认了精确的糖蛋白生物合成.
- 证明了抗原特异性IgG免疫反应,并在体内减少了细菌殖民.
结论:
- 开发了一种基于细菌细胞的强大的糖基平台,用于糖蛋白生物合成.
- 优化的策略为生产其他有价值的葡萄糖蛋白提供了指导方针.
- 合成的葡萄糖蛋白显示出作为针对UPEC O21.21的疫苗候选人的承诺.
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