Factorial design in fermentation medium development for hyaluronic acid production by Streptococcus zooepidemicus

Abstract

Hyaluronic acid (HA) has biological functions of interest to medical and cosmetic industries. The optimization of a fermentation medium contributes to improve the microbial production of the polymer on a large scale and make the product more accessible to the market. Factorial design and response surface were used to evaluate the concentration of sucrose, yeast extract, glutamine, glutamate and oxalic acid on the HA production by Streptococcus zooepidemicus in shake flasks. Biomass, lactate and acetate production were also studied. Yeast extract showed to be the main significant variable for all the studied responses, showing positive effect. For the HA production, glutamine was also significant and presented a positive effect. The best condition for the polymer production was 50 g L^-1 of yeast extract and sucrose and 0.6 g L^-1 of glutamine, glutamate and oxalic acid. In this condition, the fermentation was carried out in bioreactor with pH controlled at 8 and 0.5 vvm. HA production in bioreactor was explained by logistic regression model and the maximum concentration asymptotic of HA was 0.860 g L^-1. An increase of 34% on polymer production was observed when compared to shake flask assay. Thus, it was possible to optimize the polymer production using statistical techniques.