Enhancing acid tolerance of Escherichia coli via viroporin-mediated export of protons and its application for efficient whole-cell biotransformation

Jonghyeok Shin, Yong Su Jin, Young Cheol Park, Jin Byung Park, Young Oh Lee, Sun Ki Kim, Dae Hyuk Kweon

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Escherichia coli-based whole-cell biocatalysts are widely used for the sustainable production of value-added chemicals. However, weak acids present as substrates and/or products obstruct the growth and fermentation capability of E. coli. Here, we show that a viroporin consisting of the influenza A matrix-2 (M2) protein, is activated by low pH and has proton channel activity in E. coli. The heterologous expression of the M2 protein in E. coli resulted in a significant increase in the intracellular pH and cell viability in the presence of various weak acids with different lengths of carbon chains. In addition, the feasibility of developing a robust and efficient E. coli-based whole-cell biocatalyst via introduction of the proton-selective viroporin was explored by employing (Z)-11-(heptanolyoxy)undec-9-enoic acid (ester) and 2-fucosyllactose (2′-FL) as model products, whose production is hampered by cytosolic acidification. The engineered E. coli strains containing the proton-selective viroporin exhibited approximately 80% and 230% higher concentrations of the ester and 2′-FL, respectively, than the control strains without the M2 protein. The simple and powerful strategy developed in this study can be applied to produce other valuable chemicals whose production involves substrates and/or products that cause cytosolic acidification.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalMetabolic Engineering
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. 2020R1A2C2101964 and 2017R1A6A1A03015642 ). This research was also supported by the Chung-Ang University Graduate Research Scholarship ( Academic scholarship for College of Biotechnology and Natural Resources ) in 2021.

Publisher Copyright:
© 2021 International Metabolic Engineering Society


  • (Z)-11-(heptanolyoxy)undec-9-enoic acid
  • 2′-Fucosyllactose
  • Acid tolerance
  • Influenza A matrix-2 protein
  • Whole-cell biotransformation


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