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Chaperone and foldase coexpression in the baculovirus-insect cell expression system

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Conclusions

The BEVS has become widely utilized for production of recombinant proteins. However, protein aggregation and inefficient processing often limit yields, especially for secreted and membrane proteins. Since many proteins of pharmaceutical interest require similar posttranslational processing steps, engineering the folding, assembly, and secretion pathway may enhance the production of a wide variety of valuable complex proteins. Efforts should be undertaken to coexpress the relevant chaperones or foldases at low levels in concert with the final product to ensure the ideal folding and assembly environment. In the future, expression of oligosaccharide modifying enzymes and secretion factors may further improve secretion rates of assembled proteins and provide heterologous proteins with altered glycoforms. Also significant is the use of BEVS as an in vivo eucaryotic laboratory to study the fundamental roles of differnt chaperones, foldases, and secretion factors. The coexpression of chaperones and foldases will complement other approaches such as the development of alternative insect cell lines, promoters, and signal peptides to optimize the baculovirus-insect cell expression system for generating high yields of valuable proteins.

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Abbreviations

BEVS:

Baculovirus expression vector system

BiP:

immunoglobulin heavy chain binding protein

ELISA:

Enzyme-linked immunosorbent assay

ER:

Endoplasmic reticulum

GRP:

Glucose regulated protein

Hsp:

Heat shock protein

IgG:

Immunoglobulin G

PDI:

Protein Disulfide Isomerase

PPI:

Peptidyl-prolyl cis-trans isomerase

Sf-9:

Spodoptera frugeperda

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  1. Paul Hinderliter

    Present address: Department of Chemical Engineering, Pennsylvania State University, 16802, PA, U.S.A.

  2. Tsu-An Hsu

    Present address: Human Genome Sciences, Inc., 9410 Key West Ave., 20850, Rockville, MD, U.S.A.

Authors and Affiliations

  1. Department of Chemical Engineering, The Johns Hopkins University, 21218-2694, Baltimore, Maryland, U.S.A.

    Michael J. Betenbaugh, Eric Ailor, Erik Whiteley, Paul Hinderliter & Tsu-An Hsu

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Betenbaugh, M.J., Ailor, E., Whiteley, E. et al. Chaperone and foldase coexpression in the baculovirus-insect cell expression system. Cytotechnology 20, 149–159 (1996). https://doi.org/10.1007/BF00350396

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