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Objectives <p>To enhance hyaluronic acid (HA) production in <i>Escherichia coli</i> by utilizing <i>hasA</i> genes from <i>Streptococcus pyogenes</i> and <i>Streptococcus parauberis</i>, and employing metabolic engineering strategies.</p> Results <p>The expression of the <i>hasA</i> (<i>SpaHasA</i>) gene from <i>S. parauberis</i> in <i>E. coli</i> K12 W3110 led to higher HA production compared to the other gene. Knockout of the <i>zwf</i> and <i>pfkA</i> genes in the engineered <i>E. coli</i> expressing <i>SpaHasA</i> gene, further increased HA production to 891&#xa0;mg&#xa0;l<sup>−1</sup>. Overexpression of the <i>galU</i> and <i>ugd</i> genes in the <i>zwf</i> and <i>pfkA</i> double mutant harboring the <i>SpaHasA</i> gene elevated HA output to 1017&#xa0;mg&#xa0;l<sup>−1</sup>. Using the same engineered <i>E. coli</i> strain, optimizing the MgSO<sub>4</sub> concentration in the culture medium enhanced production to 1187&#xa0;mg&#xa0;l<sup>−1</sup>, and in fed-batch fermentation, it achieved 2283&#xa0;mg&#xa0;HA&#xa0;l<sup>−1</sup>.</p> Conclusions <p>The <i>hasA</i> genes from various <i>Streptococcus</i> groups, especially <i>S. parauberis</i>, significantly boost HA production in <i>E. coli</i>, demonstrating their potential for microbial fermentation applications.</p>

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Metabolic engineering of Escherichia coli for enhanced production of hyaluronic acid

  • 期刊论文

  • 发表日期：

    2025年3月14日

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  • Syafira Rizqi Eskasalam,
  • Selim Ashoor,
  • Hyeon Jeong Seong,
  • Yu-Sin Jang

摘要

Objectives

To enhance hyaluronic acid (HA) production in Escherichia coli by utilizing hasA genes from Streptococcus pyogenes and Streptococcus parauberis, and employing metabolic engineering strategies.

Results

The 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.

Conclusions

The hasA genes from various Streptococcus groups, especially S. parauberis, significantly boost HA production in E. coli, demonstrating their potential for microbial fermentation applications.