Physiological mechanism of the overproduction of ε-poly-L-lysine by acidic pH shock in fed-batch fermentation.

The introduction of an environmental stress of acidic pH shock had successfully solved the common deficiency existed in ε-PL production, viz. the distinct decline of ε-PL productivity in the feeding phase of the fed-batch fermentation. To unravel the underlying mechanism, we comparatively studied the physiological changes of Streptomyces sp. M-Z18 during fed-batch fermentations with the pH shock strategy (PS) and pH non-shock strategy (PNS). Morphology investigation showed that pellet-shape change was negligible throughout both fermentations. In addition, the distribution of pellet size rarely changed in the PS, whereas pellet size and number decreased substantially with time in the PNS. This was consistent with the performances of ε-PL productivity in both strategies, demonstrating that morphology could be used as a predictor of ε-PL productivity during fed-batch fermentation. Furthermore, a second growth phase happened in the PS after pH shock, followed by the re-appearance of live mycelia in the dead core of the pellets. Meanwhile, mycelia respiration and key enzymes in the central metabolic and ε-PL biosynthetic pathways were overall strengthened until the end of the fed-batch fermentation. As a result, the physiological changes induced by the acidic pH shock have synergistically and permanently contributed to the stimulation of ε-PL productivity. However, this second growth phase and re-appearance of live mycelia were absent in the PNS. These results indicated that the introduction of a short-term suppression on mycelia physiological metabolism would guarantee the long-term high ε-PL productivity.