AUTHOR=Li Mengting , Wang Zhenyu , Zhou Miao , Zhang Chong , Zhi Kaiqi , Liu Shuli , Sun Xiujuan , Wang Zhi , Liu Jinle , Liu Dong 

TITLE=Continuous Production of Human Epidermal Growth Factor Using Escherichia coli Biofilm

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.855059

DOI=10.3389/fmicb.2022.855059

ISSN=1664-302X

ABSTRACT=<p>Increasing demand for recombinant proteins necessitates efficient protein production processes. In this study, a continuous process for human epidermal growth factor (hEGF) secretion by <italic>Escherichia coli</italic> was developed by taking advantage of biofilm formation. Genes <italic>bcsB</italic>, <italic>fimH</italic>, and <italic>csgAcsgB</italic> that have proved to facilitate biofilm formation and some genes <italic>moaE</italic>, <italic>yceA</italic>, <italic>ychJ</italic>, and <italic>gshB</italic> potentially involved in biofilm formation were examined for their effects on hEGF secretion as well as biofilm formation. Finally, biofilm-based fermentation processes were established, which demonstrated the feasibility of continuous production of hEGF with improved efficiency. The best result was obtained from <italic>ychJ</italic>-disruption that showed a 28% increase in hEGF secretion over the BL21(DE3) wild strain, from 24 to 32 mg/L. Overexpression of <italic>bcsB</italic> also showed great potential in continuous immobilized fermentation. Overall, the biofilm engineering here represents an effective strategy to improve hEGF production and can be adapted to produce more recombinant proteins in future.</p>