1. Hypersecretion of OmlA antigen in Corynebacterium glutamicum through high-throughput based development process.
- Author
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Sun, Manman, Gao, Alex Xiong, Ledesma-Amaro, Rodrigo, Li, An, Wang, Rongbin, Nie, Jianqi, Zheng, Pei, Yang, Yankun, Bai, Zhonghu, and Liu, Xiuxia
- Subjects
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CORYNEBACTERIUM glutamicum , *MASS transfer coefficients , *ACTINOBACILLUS pleuropneumoniae , *ANTIGENS , *MICROPLATES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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