Review

Towards the development of Bacillus subtilis as a cell factory for membrane proteins and protein complexes

Jessica C Zweers¹ , Imrich Barák² , Dörte Becher³ , Arnold JM Driessen⁴ , Michael Hecker³ , Vesa P Kontinen⁵ , Manfred J Saller⁴ , L'udmila Vavrová² and Jan Maarten van Dijl¹

¹  Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, The Netherlands

²  Institute of Molecular Biology, Slovak Academy of Sciences, Dubravska cesta 21, 84554 Bratislava 45, Slovak Republic

³  Institute for Microbiology, F.L. Jahnstr. 15, D17487 Greifswald, Germany

⁴  Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands

⁵  Infection Pathogenesis Laboratory, Department of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland

author email corresponding author email

Microbial Cell Factories 2008, 7:10doi:10.1186/1475-2859-7-10

Published:	4 April 2008

Abstract

Background

The Gram-positive bacterium Bacillus subtilis is an important producer of high quality industrial enzymes and a few eukaryotic proteins. Most of these proteins are secreted into the growth medium, but successful examples of cytoplasmic protein production are also known. Therefore, one may anticipate that the high protein production potential of B. subtilis can be exploited for protein complexes and membrane proteins to facilitate their functional and structural analysis. The high quality of proteins produced with B. subtilis results from the action of cellular quality control systems that efficiently remove misfolded or incompletely synthesized proteins. Paradoxically, cellular quality control systems also represent bottlenecks for the production of various heterologous proteins at significant concentrations.

Conclusion

While inactivation of quality control systems has the potential to improve protein production yields, this could be achieved at the expense of product quality. Mechanisms underlying degradation of secretory proteins are nowadays well understood and often controllable. It will therefore be a major challenge for future research to identify and modulate quality control systems of B. subtilis that limit the production of high quality protein complexes and membrane proteins, and to enhance those systems that facilitate assembly of these proteins.