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
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 efcient
production.
Results Here, we optimized the fermentative production process. Following successful simplifcation 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 Ptac pedACDCg 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 Ptuf
pedACDCg allowed successful production without the need for IPTG.
Conclusions The achieved pediocin titer surpasses previous eforts 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
