Metabolic engineering of <i>Escherichia coli</i> for enhanced production of hyaluronic acid

Abstract

ObjectivesTo enhance hyaluronic acid (HA) production in Escherichia coli by utilizing hasA genes from Streptococcus pyogenes and Streptococcus parauberis, and employing metabolic engineering strategies.ResultsThe expression of the hasA (SpaHasA) gene from S. parauberis in E. coli K12 W3110 led to higher HA production compared to the other gene. Knockout of the zwf and pfkA genes in the engineered E. coli expressing SpaHasA gene, further increased HA production to 891 mg l-1. Overexpression of the galU and ugd genes in the zwf and pfkA double mutant harboring the SpaHasA gene elevated HA output to 1017 mg l-1. Using the same engineered E. coli strain, optimizing the MgSO4 concentration in the culture medium enhanced production to 1187 mg l-1, and in fed-batch fermentation, it achieved 2283 mg HA l-1.ConclusionsThe hasA genes from various Streptococcus groups, especially S. parauberis, significantly boost HA production in E. coli, demonstrating their potential for microbial fermentation applications.