A Novel Approach to the Production of Hyaluronic Acid by Streptococcus zooepidemicus

It has been shown that the initial conditions of bacterial cultivation are extremely important for the successful production of hyaluronic acid (HA) by fermentation. We investigated several parameters that affect cell growth rate and the productivity and molecular weight of hyaluronic acid--i.e., agitation speed, aeration rate, culture temperature, pH, and pressure--to determine how to optimize the production of HA by Streptococcus zooepidemicus on an industrial scale. Using a 30-1 jar fermentor under laboratory conditions, we achieved maximum HA productivity and biomass when the agitation speed and aeration rate were increased simultaneously. By shifting the temperature downward from 35$^{\circ}C$ to 32$^{\circ}C$ at key levels of cell growth during the fermentation process, we were able to obtain HA with a molecular weight of $2.8{\times}10^6$ at a productivity of 5.3 g/l. Moreover, we reproduced these optimized conditions successfully in three 30-1 jar fermentors. By reproducing these conditions in a 3-$m^3$ fermentor, we were able to produce HA with a molecular weight of $2.9{\times}10^6$ at a productivity of 5.4 g/l under large-scale conditions.