Recent Advances in High Cell Density Cultivation for Production of Recombinant Protein

Abstract

This paper reviews recent strategies used for increasing specific yield and productivity in high cell density cultures. High cell density cultures offer an efficient means for the economical production of recombinant proteins. However, there are still some challenges associated with high cell density cultivation (HCDC) techniques. A variety of strategies in several aspects including host design consideration, tuning recombinant protein expression, medium composition, growth methodologies, and even control and analysis of the process have been successfully employed by biotechnologists to increase yield in high cell density cultures. Although most researches have focused on Escherichia coli, other microorganisms have the potential to be grown at high density and need further investigation. In recent years, information on physiological changes of hosts during different phases of cultivation derived from functional genomics, transcriptomics and proteomics is being used to overcome the obstacles encountered in high cell density cultivation and hence increase productivity.