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The Problem of Expression of Multidisulfide Bonded Recombinant Proteins in E. coli

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Folding of Disulfide Proteins

Part of the book series: Protein Reviews ((PRON,volume 14))

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Abstract

Recombinant proteins currently play an important role in the pharmaceutical industry. Very frequently, proteins of therapeutic value contain complex disulfide bond patterns that are necessary for folding, stability, and/or function. Although the folding of proteins with multiple disulfide bonds in E. coli poses considerable challenges, a number of approaches developed in recent years can now be deployed for the production of such proteins at significant yields. Here, we present a summary of disulfide bond formation in E. coli and the main strategies aimed toward optimization of multidisulfided recombinant protein expression by secretion into the periplasmic space, expression in the cytoplasm of strains engineered to favor the formation of disulfide bonds in that compartment, and finally cell-free synthesis.

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Abbreviations

AP:

Alkaline phosphatase

BPTI:

Bovine pancreatic trypsin inhibitor

CHO:

Chinese hamster ovary

DTT:

Dithiothreitol

ER:

Endoplasmic reticulum

FDA:

Food and drug administration

GAPDH:

d-Glyceraldehyde-3-phosphate dehydrogenase

GSH:

Glutathione

GSSG:

Glutathione disulfide

GST:

Glutathione S-transferase

l-Arg:

l-Arginine

l-Glu:

l-Glutamine

MBP:

Maltose-binding protein

NADPH:

Nicotinamide adenine dinucleotide phosphate reduced

scFv:

Single-chain fragment variable antibody

Sec-pathway:

Secretory pathway

SRP:

Signal recognition particle

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Texas, Austin, TX, 78712, USA

    Silvia A. Arredondo & George Georgiou

  2. Department of Biomedical Engineering, University of Texas, Austin, TX, 78712, USA

    George Georgiou

  3. Department of Molecular Genetics and Microbiology, University of Texas, Austin, TX, 78712, USA

    George Georgiou

  4. Institute for Cell and Molecular Biology, University of Texas, Austin, TX, 78712, USA

    George Georgiou

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  1. Silvia A. Arredondo
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  2. George Georgiou
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Correspondence to George Georgiou .

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  1. Brown Foundation Inst. of Molecular Medi, The University of Texas, Houston, 77030, Texas, USA

    Rowen J. Y. Chang

  2. Institut de Biotecnologia i de Biomed., Dept. de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain

    Salvador Ventura

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Arredondo, S.A., Georgiou, G. (2011). The Problem of Expression of Multidisulfide Bonded Recombinant Proteins in E. coli . In: Chang, R., Ventura, S. (eds) Folding of Disulfide Proteins. Protein Reviews, vol 14. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7273-6_9

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