Bioreactor Systems for Efficient Production and Separation of Nisin Z Using Lactococcus lactis IO-1

Continuous fermentation was introduced to improve the nisin Z productivity of Lactococcus lactis IO-1. Free cells showed a good productivity at the dilution rate of 0.1h^-1. However, nisin Z production was affected by cell wash-out at the dilution rate of 0.2h^-1. Continuous fermentation with the cells adsorbed on ENTG-3800 gel beads displayed an improvement in productivity at higher dilution rates. No enhancement of nisin Z production was observed during continuous fermentation at a high cell density employing a hydrophobic hollow fiber membrane. The polyolefin membrane adsorbed the produced nisin Z too much. Continuous fermentation at a high cell density employing a ceramic membrane displayed a good nisin Z productivity at high dilution rates. Nisin Z productivity could be increased if a ceramic membrane with an adequate and effective filtration area is employed. Nisin Z was separated from the fermentation broth using various kinds of adsorbents including Amberlite IR-120B, CM Sephadex C-25, Celite, and Sep-Pak cartridges. The Sep-Pak (tC₁₈, C₁₈, C₈, and tC₂) cartridges showed a substantial capacity for nisin Z adsorption. A moderate reversed-phase column, a Sep-Pak C₈ cartridge, was applied to integrate nisin Z fermentation with a ceramic membrane and product separation system. Nisin Z productivity was enhanced by the integration of the nisin Z adsorption cartridge. This result indicates the possibility of continuous fermentation with the integrated bioreactor system followed by high nisin Z productivity.