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Recombinant protein solubility—does more mean better?

Nature Biotechnology volume 25, pages 718–720 (2007)Cite this article

To the editor:

Inclusion bodies have long been regarded as clusters of polypeptides unable to reach native conformation that are deposited as inert reservoirs sequestered from protease activity. An increasing number of reports indicate that bacterial inclusion bodies comprise proteins in different conformations, a significant proportion of which may be biologically active. For example, a pioneering study in 1989 by Worrall and Goss3 showed that inclusion bodies formed by Escherichia coli β-galactosidase exhibit specific activities around one-third of those shown by soluble enzyme. Other enzymes, produced alone or as fusion proteins, form inclusion bodies that are also biologically active (for a review, see ref. 4). Our group5 and others6 have demonstrated this occurs not only in the cytoplasm, but also in the periplasm if secreted. In some cases, the specific activities of the aggregated and soluble enzyme versions are very close5. Similarly, work by our group5,7 and others8 at the Institute for Biotechnology and Biomedicine has shown that fluorescent proteins (e.g., green fluorescent protein (GFP), blue fluorescent protein and derived fusions) form inclusion bodies that remain highly fluorescent.

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Figure 1: The functionality of recombinant proteins aggregated as inclusion bodies.

References

  1. Baneyx, F. & Mujacic, M. Nat. Biotechnol. 22, 1399–1408 (2004).

    Article  CAS  Google Scholar 

  2. Sorensen, H.P. & Mortensen, K.K. Microb. Cell Fact. 4, 1 (2005).

    Article  Google Scholar 

  3. Worrall, D.M. & Goss, N.H. Aust. J. Biotechnol 3, 28–32 (1989).

    CAS  PubMed  Google Scholar 

  4. Ventura, S. & Villaverde, A. Trends Biotechnol. 24, 179–185 (2006).

    Article  CAS  Google Scholar 

  5. Garcia-Fruitos, E. et al. Microb. Cell Fact. 4, 27 (2005).

    Article  Google Scholar 

  6. Arie, J.P., Miot, M., Sassoon, N. & Betton, J.M. Mol. Microbiol. 62, 427–437 (2006).

    Article  CAS  Google Scholar 

  7. Vera, A., Gonzalez-Montalban, N., Aris, A. & Villaverde, A. Biotechnol. Bioeng. 96, 1101–1106 (2007).

    Article  CAS  Google Scholar 

  8. de Groot, N.S. & Ventura, S. J. Biotechnol. 125, 110–113 (2006).

    Article  Google Scholar 

  9. Carrio, M., Gonzalez-Montalban, N., Vera, A., Villaverde, A. & Ventura, S. J. Mol. Biol. 347, 1025–1037 (2005).

    Article  CAS  Google Scholar 

  10. Waldo, G.S., Standish, B.M., Berendzen, J. & Terwilliger, T.C. Nat. Biotechnol. 17, 691–695 (1999).

    Article  CAS  Google Scholar 

  11. Garcia-Fruitos, E., Carrio, M.M., Aris, A. & Villaverde, A. Biotechnol. Bioeng. 90, 869–875 (2005).

    Article  CAS  Google Scholar 

  12. Gonzalez-Montalban, N., Garcia-Fruitos, E., Ventura, S., Aris, A. & Villaverde, A. Microb. Cell Fact. 5, 26 (2006).

    Article  Google Scholar 

  13. de Marco, A. & Schroedel, A. BMC Biochem. 6, 10 (2005).

    Article  Google Scholar 

  14. Carrio, M.M. & Villaverde, A. J. Bacteriol. 187, 3599–3601 (2005).

    Article  CAS  Google Scholar 

  15. Garcia-Fruitos, E., Aris, A., & Villaverde, A. Appl. Environ. Microbiol. 73, 289–294 (2007).

    Article  CAS  Google Scholar 

  16. Martinez-Alonso, M., Vera, A. & Villaverde, A. FEMS Microbiol. Lett., published online 11 June 2007, doi: 10.111/j.1574-6968.2007.00788.x

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Acknowledgements

The authors wish to acknowledge their funding for research on protein folding and aggregation (through grants BIO2004-0700 MEC and 2005SGR-00956 AGAUR, Spain). N.G.M. and E.G.F. received predoctoral fellowships from MEC. N.G.-M. and E.G.-F. contributed equally to this work.

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  1. Department of Genetics and Microbiology and CIBER in Bioengineering, Institute for Biotechnology and Biomedicine, Biomaterials and Nanomedicine, Autonomous University of Barcelona, Bellaterra, 08193, Barcelona, Spain

    Nuria González-Montalbán, Elena García-Fruitós & Antonio Villaverde

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  1. Nuria González-Montalbán
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  3. Antonio Villaverde
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González-Montalbán, N., García-Fruitós, E. & Villaverde, A. Recombinant protein solubility—does more mean better?. Nat Biotechnol 25, 718–720 (2007). https://doi.org/10.1038/nbt0707-718

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