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Towards improved resistance of Corynebacterium glutamicum against nisin

Dominik Weixler, Oliver Goldbeck, Gerd. M. Seibold, Bernhard J. Eikmanns, Christian U. Riedel
doi: https://doi.org/10.1101/2021.08.09.454123
Dominik Weixler
1Institute of Microbiology and Biotechnology, University of Ulm, Ulm, Germany
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Oliver Goldbeck
1Institute of Microbiology and Biotechnology, University of Ulm, Ulm, Germany
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Gerd. M. Seibold
2Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
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Bernhard J. Eikmanns
1Institute of Microbiology and Biotechnology, University of Ulm, Ulm, Germany
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Christian U. Riedel
1Institute of Microbiology and Biotechnology, University of Ulm, Ulm, Germany
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  • For correspondence: christian.riedel@uni-ulm.de
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Abstract

The bacteriocin nisin is one of the best studied antimicrobial peptides. It is widely used as a food preservative due to its antimicrobial activity against various Gram-positive bacteria including human pathogens such as Listeria monocytogenes and others. The receptor of nisin is the universal cell wall precursor lipid II, which is present in all bacteria. Thus, nisin has a broad spectrum of target organisms. Consequently, heterologous production of nisin with biotechnological relevant organisms including Corynebacterium glutamicum is difficult. Nevertheless, bacteria have evolved several mechanisms of resistance against nisin and other cationic antimicrobial peptides (CAMPs). Here, we transferred resistance mechanisms described in other organisms to C. glutamicum with the aim to improve nisin resistance. The presented approaches included: expression of (i) nisin immunity genes nisI and/or nisFEG or (ii) nisin ABC-transporter genes of Staphylococcus aureus and its homologues of C. glutamicum, (iii) genes coding for enzymes for alanylation or lysinylation of the cell envelope to introduce positive charges, and/or (iv) deletion of genes for porins of the outer membrane. None of the attempts alone increased resistance of C. glutamicum more than two-fold. To increase resistance of C. glutamicum to levels that will allow heterologous production of active nisin at relevant titers, further studies are needed.

Competing Interest Statement

Dominik Weixler, Oliver Goldbeck, Gerd M. Seibold, and Christian U. Rriedel are co-inventors on a patent application related to this research.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 09, 2021.
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Towards improved resistance of Corynebacterium glutamicum against nisin
Dominik Weixler, Oliver Goldbeck, Gerd. M. Seibold, Bernhard J. Eikmanns, Christian U. Riedel
bioRxiv 2021.08.09.454123; doi: https://doi.org/10.1101/2021.08.09.454123
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Towards improved resistance of Corynebacterium glutamicum against nisin
Dominik Weixler, Oliver Goldbeck, Gerd. M. Seibold, Bernhard J. Eikmanns, Christian U. Riedel
bioRxiv 2021.08.09.454123; doi: https://doi.org/10.1101/2021.08.09.454123

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