This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Zweers, J. C.
Right arrow Articles by van Dijl, J. M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zweers, J. C.
Right arrow Articles by van Dijl, J. M.
Agricola
Right arrow Articles by Zweers, J. C.
Right arrow Articles by van Dijl, J. M.

 Previous Article  |  Next Article 

Applied and Environmental Microbiology, December 2009, p. 7356-7364, Vol. 75, No. 23
0099-2240/09/$08.00+0     doi:10.1128/AEM.01560-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Stress-Responsive Systems Set Specific Limits to the Overproduction of Membrane Proteins in Bacillus subtilis{triangledown},{dagger}

Jessica C. Zweers,1 Thomas Wiegert,2 and Jan Maarten van Dijl1*

Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands,1 Institute of Genetics, University of Bayreuth, D-95440 Bayreuth, Germany2

Received 2 July 2009/ Accepted 28 September 2009

Essential membrane proteins are generally recognized as relevant potential drug targets due to their exposed localization in the cell envelope. Unfortunately, high-level production of membrane proteins for functional and structural analyses is often problematic. This is mainly due to their high overall hydrophobicity. To develop new concepts for membrane protein overproduction, we investigated whether the biogenesis of overproduced membrane proteins is affected by stress response-related proteolytic systems in the membrane. For this purpose, the well-established expression host Bacillus subtilis was used to overproduce eight essential membrane proteins from B. subtilis and Staphylococcus aureus. The results show that the {sigma}W regulon (responding to cell envelope perturbations) and the CssRS two-component regulatory system (responding to unfolded exported proteins) set critical limits to membrane protein production in large quantities. The identified sigW or cssRS mutant B. subtilis strains with significantly improved capacity for membrane protein production are interesting candidate expression hosts for fundamental research and biotechnological applications. Importantly, our results pinpoint the interdependent expression and function of membrane-associated proteases as key parameters in bacterial membrane protein production.

* Corresponding author. Mailing address: Department of Medical Microbiology, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Phone: 31-50-3615187. Fax: 31-50-3619105. E-mail: J.M.van.Dijl{at}med.umcg.nl

{triangledown} Published ahead of print on 9 October 2009.

{dagger} Supplemental material for this article may be found at http://aem.asm.org/.

Applied and Environmental Microbiology, December 2009, p. 7356-7364, Vol. 75, No. 23
0099-2240/09/$08.00+0     doi:10.1128/AEM.01560-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»