A quantitative interpretation of oxidative protein folding activity in Escherichia coli
Microbial cell factories(2022)
Abstract
Background Escherichia coli is of central interest to biotechnological research and a widely used organism for producing proteins at both lab and industrial scales. However, many proteins remain difficult to produce efficiently in E. coli . This is particularly true for proteins that require post translational modifications such as disulfide bonds. Results In this study we develop a novel approach for quantitatively investigating the ability of E. coli to produce disulfide bonds in its own proteome. We summarise the existing knowledge of the E. coli disulfide proteome and use this information to investigate the demand on this organism’s quantitative oxidative folding apparatus under different growth conditions. Furthermore, we built an ordinary differential equation-based model describing the cells oxidative folding capabilities. We use the model to infer the kinetic parameters required by the cell to achieve the observed oxidative folding requirements. We find that the cellular requirement for disulfide bonded proteins changes significantly between growth conditions. Fast growing cells require most of their oxidative folding capabilities to keep up their proteome while cells growing in chemostats appear limited by their disulfide bond isomerisation capacities. Conclusion This study establishes a novel approach for investigating the oxidative folding capacities of an organism. We show the capabilities and limitations of E. coli for producing disulfide bonds under different growth conditions and predict under what conditions excess capability is available for recombinant protein production.
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Key words
Disulfide bond formation,Disulfide proteome,Escherichia coli,Kinetic modelling,Oxidative folding,Recombinant protein production,Systems biology
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