Bioprocess and Biosystems Engineering

Chinese hamster ovary (CHO) cells are the main workhorse in the biopharmaceutical industry for the production of recombinant proteins, such as monoclonal antibodies. To date, a variety of metabolic engineering approaches have been used to improve the productivity of CHO cells. While genetic manipulations are potentially laborious in mammalian cells, rational design of CHO cell culture medium or efficient fed-batch strategies are more popular approaches for bioprocess optimization. In this study, a genome-scale metabolic network model of CHO cells was used to design feeding strategies for CHO cells to improve monoclonal antibody (mAb) production. A number of metabolites, including threonine and arachidonate, were suggested by the model to be added into cell culture medium. The designed composition has been experimentally validated, and then optimized, using design of experiment methods. About a two-fold increase in the total mAb expression has been observed using this strategy. Our approach can be used in similar bioprocess optimization problems, to suggest new ways of increasing production in different cell factories.

The thermal stability of an immobilization technique using a pellicular latex matrix was examined in a packed-bed column reactor. The stability was found to vary with liquid flow rate, the type of latex, temperature of operation, and the amount of yeast cells. Adjusting these parameters and introducing particulate inorganic fillers strengthened the latex matrix and improved the thermal stability. Optimization of this immobilization technique resulted in a procedure that allowed latex polymers to be mechanically stable at temperatures up to 50°C. The biological viability of this improved immobilization scheme was demonstrated through the production of L-aspartic acid by immobilized cells of E. coli.

 This paper reports the influence of sulfate-reducing bacterial activity on acidogenic digestion of waste activated sludge (WAS). A series of experiments was conducted by feeding WAS to a 10-l, completely mixed, mesophilic reactor maintained at pH 5.0 under sulfidogenic and non-sulfidogenic conditions. Analyses of volatile fatty acids indicated that the productions of acetic and propionic acids were slightly increased by sulfidogenic activity at 218 mg/l level of sulfate when COD sulfate ratio was 55:1. Higher amounts of methanol, ethanol and hydrogen were observed in the non-sulfidogenic condition, but ammonia was lower than in the moderate sulfidogenic runs. At 0.63 kg VS/m3 d loading rate the hydrolysis was above 90% in both moderate sulfidogenic and non- sulfidogenic runs. The results of these experiments showed the possible influence of moderate sulfidogenesis in the protein degradation of WAS anaerobic digestion. However, the acid-phase digestion was adversely affected by increasing the sulfate concentration to 400 mg/l.