High density cell culture study of microorganisms was carried out using a membrane cell recycle fermenter. The hollow fiber membrane filter is attached to the stirred fermenter and the cell broth is recirculated through the filter unit. The product is continuously removed as filtrate and the cells are recycled to the fermenter. Filter performance is important in this system and is highly dependent on linear velocity along the hollow fiber.
The ethanol fermentation by Saccharomyces cerevisiae was carried out. Maximum biomass concentrations up to 210 g-dry wt/L were obtained, but in normal operation concentrations were between 100 and 150 g/L. The ethanol productivity was 85 g/L.h, with an ethanol concentration of 65 g/L and an ethanol yield over 90%. The ethanol productivity and yeast growth rate decreased as the cell concentration increased beyond a certain level. The cell mass in the reactor was maintained by a proper manipulation of dilution rate and bleed ratio depending on the growth rate.
Escherichia coli haboring recombinant plasmid and having high tryptophan production activity was cultivated in this system. The maximum cell concentration increased tenfold compared to that in conventional batch process. The main inhibitory metabolic product was acetic acid, which accumulated to 13.5 g/L and inhibited the cell growth. The volumetric productivity of tryptophan was about 0.085 g/L.h. The stability of recombinant rapidly declined as the cell concentration increased during the recycle operation.
The wild type E. coli was also cultivated. No metabolic fatty acid accumulated and the cell concentration reached to 95 g/L.