Enhanced production of nukacin D13E in Lactococcus lactis NZ9000 by the additional expression of immunity genes

• Published in: Applied microbiology and biotechnology 2012-01, Vol.93 (2), p.671-678
• Main Authors: Puramattathu, Tijo Varghese, Islam, Mohammad R., Nishie, Mami, Yanagihara, Sae, Nagao, Jun-ichi, Okuda, Ken-ichi, Zendo, Takeshi, Nakayama, Jiro, Sonomoto, Kenji
• Format: Article
• Language: English
• Subjects: ABC transporter; ABC transporters; Amino acids; Antibiotics; Antimicrobial agents; Applied Genetics and Molecular Biotechnology; Bacteria; Bacteriocins - genetics; Bacteriocins - metabolism; Biological Transport; Biomedical and Life Sciences; Biotechnology; Drug Resistance, Bacterial; Fermentation; Gene Expression; Gram-positive bacteria; Immunology; Laboratories; Lactococcus lactis; Lactococcus lactis - genetics; Lactococcus lactis - metabolism; Life Sciences; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Microbial Genetics and Genomics; Microbiology; Mutagenesis; Mutant Proteins - genetics; Mutant Proteins - metabolism; Mutation, Missense; Peptides; Plasmids; Polymerase chain reaction; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Studies
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-011-3563-1

Nukacin D13E (D13E) is a variant of type-A(II) lantibiotic nukacin ISK-1 produced by Staphylococcus warneri ISK-1. D13E exhibited a twofold higher specific antimicrobial activity than nukacin ISK-1 against a number of Gram-positive bacteria. We previously reported the heterologous production of D13E in Lactococcus lactis NZ9000 under the control of nisin-controlled gene expression system. In this study, we demonstrated enhanced production of D13E by the additional expression of immunity genes, nukFEG . The nukacin ISK-1 immunity, conferred by the ABC transporter complex, NukFEG, and the lantibiotic-binding protein, NukH, was not overwhelmed by D13E. The additional NukFEG resulted in a fourfold increase in the immunity level of the strain and a 5.2-fold increase in D13E production. The additional NukFEGH-expressing strain with the highest D13E immunity showed reduced level of production. Further improvement in D13E production was achieved by using pH-controlled batch fermentation.