Production of hyaluronic acid by repeated batch fermentation

The production of hyaluronic acid (HA) by Streptococcus zooepidemicus with repeated batch fermentation has been investigated. It was found that, with conventional operation, both maximal specific growth rate (μm) and specific HA productivity (YP/X) decreased with increasing seed volume, suggesting that there exist some inhibitors in the broth. The removal of liquid in the seed was first attempted by installing nonwoven fabrics (NWF) in the fermentor to retain some of the cells when draining the broth. However, this resulted in a loss of HA productivity, which in turn was attributed to the growth of a sticky, non-HA-producing mutant on the NWF. Using an external cartridge filter to partially retain the cells, followed by back-washing the filter with fresh medium for seeding, μm and YP/X could be maintained successfully at their batch levels during the repeated cycles. In an operation that seeded 31% cell, the volumetric production rate of the repeated batch culture (0.59 g HA L−1 h−1) was found to be 2.5-fold of the batch culture (0.24 g HA L−1 h−1).