Hypersecretion of vaccine antigen outer membrane lipoprotein A 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.