Biotechnology and Bioengineering, Vol.59, No.3, 379-385, 1998
Improvement of heterologous protein productivity using recombinant Yarrowia lipolytica and cyclic fed-batch process strategy
A cyclic fed-batch bioprocess is designed and a significant improvement of rice alpha-amylase productivity of recombinant Yarrowia lipolytica is illustrated. A bioprocess control strategy developed and reported here entails use of a genetically stable recombinant cloned for heterologous protein, use of optimized media for cell growth and enzyme production phases, and process control strategy enabling high cell-density culture and high alpha-amylase productivity. This process control can be achieved through maintaining a constant optimal specific cell growth rate at a predetermined value (i.e., 0.1 h(-1)), controlling medium feed rate commensurate with the cell growth rate, and maintaining a high cell-density culture (i.e., 60-70 g/L) for high productivity of cloned heterologous protein. The volumetric enzyme productivity (1,960 units/L.h) achieved from the cyclic fed-batch process was about 3-fold higher than that of the fed-batch culture process (630 units/L.h).