Unlike mixed carbon source strategies using glucose and glycerol
as co-substrates, lactobionic acid biosynthesis was stimulated
in a whey/lactose co-fermentation (Fig. 3C). Lactose feeding
enabled to increase the lactose availability above 50 g/L just at
the onset of the lactobionic acid production phase. Such effect
was also translated into higher metabolic activities, which contributed
to improved cellular robustness during the lactobionic
acid overproduction phase. Specifically, lactobionic acid overproduction
was associated with the increase in the membrane depolarization
status and metabolic activity even at later cultivation
stages (48 h). Whereas glycerol and glucose feedings promoted cell
biomass formation without increasing the cell metabolic activity
levels, lactose co-supply conversely stimulated the lactose oxidation
while supporting high biological performance and cellular
robustness (Fig. 6).