Genetic or chemical protease inhibition causes significant changes in the Bacillus subtilis exoproteome
| Autor: | David Noone, Helga Westers, Kevin M. Devine, Geeske Zanen, Wim J. Quax, Lidia Westers, Haike Antelmann, Michael Hecker, Jan Maarten van Dijl |
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| Přispěvatelé: | Translational Immunology Groningen (TRIGR), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Nanotechnology and Biophysics in Medicine (NANOBIOMED) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Proteomics
Proteases STRESS Proteome GRAM-POSITIVE BACTERIA UNFOLDED PROTEINS medicine.medical_treatment Mutant Bacillus subtilis exoproteome Biochemistry DEFICIENT Bacterial Proteins Endopeptidases Extracellular medicine Secretion Protease Inhibitors Molecular Biology chemistry.chemical_classification Protease EXPRESSION-SECRETION SYSTEM biology HETEROLOGOUS PRODUCTION HEAT-SHOCK alpha-amylase Gene Expression Regulation Bacterial DEGRADATION biology.organism_classification 2-COMPONENT REGULATORY SYSTEM protease inhibition secretome Secretory protein Enzyme chemistry ESCHERICHIA-COLI interleukin-3 Periplasmic Proteins |
| Zdroj: | Proteomics, 8(13), 2704-2713. Wiley |
| ISSN: | 1615-9853 |
| Popis: | Bacillus subtilis is a prolific producer of enzymes and biopharmaceuticals. However, the susceptibility of heterologous proteins to degradation by (extracellular) proteases is a major limitation for use of B. subtilis as a protein cell factory. An increase in protein production levels has previously been achieved by using either protease-deficient strains or addition of protease inhibitors to B. subtilis cultures. Notably, the effects of genetic and chemical inhibition of proteases have thus far not been compared in a systematic way. In the present studies, we therefore compared the exoproteomes of cells in which extracellular proteases were genetically or chemically inactivated. The results show substantial differences in the relative abundance of various extracellular proteins. Furthermore, a comparison of the effects of genetic and/or chemical protease inhibition on the stress response triggered by (over) production of secreted proteins showed that chemical protease inhibition provoked a genuine secretion stress response. From a physiological point of view, this suggests that the deletion of protease genes is a better way to prevent product degradation than the use of protease inhibitors. Importantly however, studies with human interleukin-3 show that chemical protease inhibition can result in improved production of protease-sensitive secreted proteins even in mutant strains lacking eight extracellular proteases. |
| Databáze: | OpenAIRE |
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