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).
Chang
C C
CC
Process Development Division, Development Center for Biotechnology, 81 Chang-Hsing Street, Taipei, Taiwan, Republic of China.
Ryu
D D
DD
Park
C S
CS
Kim
J Y
JY
D019149:Bioreactors; D003001:Cloning, Molecular / Q000379:methods*; D005285:Fermentation; D012275:Oryza / Q000201:enzymology; D011994:Recombinant Proteins / Q000096:biosynthesis; D004718:Saccharomycetales / Q000254:growth & development; D000516:alpha-Amylases / Q000096:biosynthesis* / Q000235:genetics
D011994:Recombinant Proteins; D000516:alpha-Amylases