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Increasing recombinant protein production in Escherichia coli through metabolic and genetic engineering

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  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Different hosts have been used for recombinant protein production, ranging from simple bacteria, such as Escherichia coli and Bacillus subtilis, to more advanced eukaryotes as Saccharomyces cerevisiae and Pichia pastoris, to very complex insect and animal cells. All have their advantages and drawbacks and not one seems to be the perfect host for all purposes. In this review we compare the characteristics of all hosts used in commercial applications of recombinant protein production, both in the area of biopharmaceuticals and industrial enzymes. Although the bacterium E. coli remains a very often used organism, several drawbacks limit its possibility to be the first-choice host. Furthermore, we show what E. coli strains are typically used in high cell density cultivations and compare their genetic and physiological differences. In addition, we summarize the research efforts that have been done to improve yields of heterologous protein in E. coli, to reduce acetate formation, to secrete the recombinant protein into the periplasm or extracellular milieu, and to perform post-translational modifications. We conclude that great progress has been made in the incorporation of eukaryotic features into E. coli, which might allow the bacterium to regain its first-choice status, on the condition that these research efforts continue to gain momentum.

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Notes

  1. However this value can vary greatly, depending on how a biopharmaceutical is defined and the sources consulted.

  2. http://www.biopharma.com/approvals.html consulted on 15 June 2011.

  3. http://www.amfep.org consulted on 17 June 2011.

  4. 1 c-mole equals 1 mole multiplied by the number of C-atoms in the molecule. This concept is used to express mass balances in biochemistry.

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Acknowledgments

This work was financially supported by the Special Research Fund (BOF) of Ghent University. The authors like to thank Jo Maertens and Joeri Beauprez for lively scientific discussions and critical comments.

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  1. Centre of Expertise–Industrial Biotechnology and Biocatalysis, Department of Biochemical and Microbial Technology, Ghent University, Coupure Links 653, 9000, Ghent, Belgium

    Hendrik Waegeman & Wim Soetaert

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Waegeman, H., Soetaert, W. Increasing recombinant protein production in Escherichia coli through metabolic and genetic engineering. J Ind Microbiol Biotechnol 38, 1891–1910 (2011). https://doi.org/10.1007/s10295-011-1034-4

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