Hypersecretion of OmlA antigen in Corynebacterium glutamicum through high-throughput based development process.

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.

• Authors: Manman Sun, Alex Xiong Gao, Rodrigo Ledesma-Amaro, An Li, Rongbin Wang, Jianqi Nie, Pei Zheng, Yankun Yang, Zhonghu Bai, Xiuxia Liu
• Journal: Applied microbiology and biotechnology (Appl Microbiol Biotechnol) Vol. 106 Issue 8 Pg. 2953-2967 (Apr 2022) ISSN: 1432-0614 [Electronic] Germany
• PMID: 35435456 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Lipoprotein(a)

Topics

• Actinobacillus pleuropneumoniae
• Animals
• Bioreactors
• Corynebacterium glutamicum (genetics, metabolism)
• Fermentation
• Lipoprotein(a) (metabolism)
• Swine