High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions
Abstract Background Pediocin PA-1 is a bacteriocin of recognized value with applications in food bio-preservation and the medical sector for the prevention of infection. To date, industrial manufacturing of pediocin PA-1 is limited by high cost and low-performance. The recent establishment of the bi...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-023-02044-y |
| _version_ | 1827982344755085312 |
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| author | Jens Christmann Peng Cao Judith Becker Christian K. Desiderato Oliver Goldbeck Christian U. Riedel Michael Kohlstedt Christoph Wittmann |
| author_facet | Jens Christmann Peng Cao Judith Becker Christian K. Desiderato Oliver Goldbeck Christian U. Riedel Michael Kohlstedt Christoph Wittmann |
| author_sort | Jens Christmann |
| collection | DOAJ |
| description | Abstract Background Pediocin PA-1 is a bacteriocin of recognized value with applications in food bio-preservation and the medical sector for the prevention of infection. To date, industrial manufacturing of pediocin PA-1 is limited by high cost and low-performance. The recent establishment of the biotechnological workhorse Corynebacterium glutamicum as recombinant host for pediocin PA-1 synthesis displays a promising starting point towards more efficient production. Results Here, we optimized the fermentative production process. Following successful simplification of the production medium, we carefully investigated the impact of dissolved oxygen, pH value, and the presence of bivalent calcium ions on pediocin production. It turned out that the formation of the peptide was strongly supported by an acidic pH of 5.7 and microaerobic conditions at a dissolved oxygen level of 2.5%. Furthermore, elevated levels of CaCl2 boosted production. The IPTG-inducible producer C . glutamicum CR099 pXMJ19 P tac pedACD Cg provided 66 mg L−1 of pediocin PA-1 in a two-phase batch process using the optimized set-up. In addition, the novel constitutive strain P tuf pedACD Cg allowed successful production without the need for IPTG. Conclusions The achieved pediocin titer surpasses previous efforts in various microbes up to almost seven-fold, providing a valuable step to further explore and develop this important bacteriocin. In addition to its high biosynthetic performance C. glutamicum proved to be highly robust under the demanding producing conditions, suggesting its further use as host for bacteriocin production. |
| first_indexed | 2024-04-09T22:32:09Z |
| format | Article |
| id | doaj.art-cfab97787c814045b17ef1d62bf181ca |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-09T22:32:09Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-cfab97787c814045b17ef1d62bf181ca2023-03-22T12:43:20ZengBMCMicrobial Cell Factories1475-28592023-02-0122111810.1186/s12934-023-02044-yHigh-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ionsJens Christmann0Peng Cao1Judith Becker2Christian K. Desiderato3Oliver Goldbeck4Christian U. Riedel5Michael Kohlstedt6Christoph Wittmann7Institute for Systems Biotechnology, Saarland UniversityInstitute for Systems Biotechnology, Saarland UniversityInstitute for Systems Biotechnology, Saarland UniversityInstitute of Microbiology and Biotechnology, University of UlmInstitute of Microbiology and Biotechnology, University of UlmInstitute of Microbiology and Biotechnology, University of UlmInstitute for Systems Biotechnology, Saarland UniversityInstitute for Systems Biotechnology, Saarland UniversityAbstract Background Pediocin PA-1 is a bacteriocin of recognized value with applications in food bio-preservation and the medical sector for the prevention of infection. To date, industrial manufacturing of pediocin PA-1 is limited by high cost and low-performance. The recent establishment of the biotechnological workhorse Corynebacterium glutamicum as recombinant host for pediocin PA-1 synthesis displays a promising starting point towards more efficient production. Results Here, we optimized the fermentative production process. Following successful simplification of the production medium, we carefully investigated the impact of dissolved oxygen, pH value, and the presence of bivalent calcium ions on pediocin production. It turned out that the formation of the peptide was strongly supported by an acidic pH of 5.7 and microaerobic conditions at a dissolved oxygen level of 2.5%. Furthermore, elevated levels of CaCl2 boosted production. The IPTG-inducible producer C . glutamicum CR099 pXMJ19 P tac pedACD Cg provided 66 mg L−1 of pediocin PA-1 in a two-phase batch process using the optimized set-up. In addition, the novel constitutive strain P tuf pedACD Cg allowed successful production without the need for IPTG. Conclusions The achieved pediocin titer surpasses previous efforts in various microbes up to almost seven-fold, providing a valuable step to further explore and develop this important bacteriocin. In addition to its high biosynthetic performance C. glutamicum proved to be highly robust under the demanding producing conditions, suggesting its further use as host for bacteriocin production.https://doi.org/10.1186/s12934-023-02044-yCorynebacterium glutamicumPediocin PA-1BioprocessFood additiveBacteriocinAntimicrobial peptide |
| spellingShingle | Jens Christmann Peng Cao Judith Becker Christian K. Desiderato Oliver Goldbeck Christian U. Riedel Michael Kohlstedt Christoph Wittmann High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions Microbial Cell Factories Corynebacterium glutamicum Pediocin PA-1 Bioprocess Food additive Bacteriocin Antimicrobial peptide |
| title | High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions |
| title_full | High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions |
| title_fullStr | High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions |
| title_full_unstemmed | High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions |
| title_short | High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions |
| title_sort | high efficiency production of the antimicrobial peptide pediocin pa 1 in metabolically engineered corynebacterium glutamicum using a microaerobic process at acidic ph and elevated levels of bivalent calcium ions |
| topic | Corynebacterium glutamicum Pediocin PA-1 Bioprocess Food additive Bacteriocin Antimicrobial peptide |
| url | https://doi.org/10.1186/s12934-023-02044-y |
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