谷氨酸棒杆菌
胸膜肺炎放线杆菌
发酵
微生物学
生物反应器
分泌物
生物
重组DNA
抗原
产量(工程)
化学
作者
Manman Sun,Alex Xiong Gao,Rodrigo Ledesma-Amaro,An Li,Rongbin Wang,Jianqi Nie,Pei Zheng,Yankun Yang,Zhonghu Bai,Xiuxia Liu
标识
DOI:10.1007/s00253-022-11918-x
摘要
Outer membrane lipoprotein A (OmlA) is a vaccine antigen against porcine contagious pleuropneumonia (PCP), a disease severely affecting the swine industry. Here, we aimed to systematically potentiate the secretory production of OmlA in Corynebacterium glutamicum (C. glutamicum), a widely used microorganism in the food industry, by establishing a holistic development process based on our high-throughput culture platform. The expression patterns, expression element combinations, medium composition, and induction conditions were comprehensively screened or optimized in microwell plates (MWPs), followed by fermentation parameter optimization in a 4 × 1 L parallel fermentation system (CUBER4). An unprecedented yield of 1.01 g/L OmlA was ultimately achieved in a 5-L bioreactor following the scaling-up strategy of fixed oxygen mass transfer coefficient (kLa), and the produced OmlA antigen showed well-protective immunity against Actinobacillus pleuropneumoniae challenge. This result provides a rapid and reliable pipeline to achieve the hyper-production of OmlA, and possibly other recombinant vaccines, in C. glutamicum. KEY POINTS: • Established a holistic development process and applied it to potentiate the secretion of OmlA. • The secretion of OmlA reached an unprecedented yield of 1.01 g/L. • The recombinant OmlA antigen induced efficient protective immunity.
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