GROWTH-BEHAVIOR OF CHINESE HAMSTER OVARY CELLS IN A COMPACT LOOP BIOREACTOR .2. EFFECTS OF MEDIUM COMPONENTS AND WASTE PRODUCTS

被引:89
作者
KURANO, N
LEIST, C
MESSI, F
KURANO, S
FIECHTER, A
机构
[1] Department of Biotechnology, Swiss Federal Institute of Technology, Zürich
关键词
Ammonia; Asparagine; Chinese hamster ovary (CHO) cell; Compact loop bioreactor; Fed-batch culture; Glucose; Glutamine;
D O I
10.1016/0168-1656(90)90055-G
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Effects of biochemical factors, i.e., medium components and metabolic byproducts, on growth of Chinese hamster ovary (CHO) cells were investigated. Glucose and ammonia were found to inhibit the growth. Kinetic analysis gave the inhibition constants, 0.14 g l-1 for ammonia and 5.0 g l-1 for glucose. Since glutamine was unstable and was a main source of ammonia, precise studies on glutamine degradation and ammonia formation process were done. By evaluating the spontaneous reactions, net glutamine utilization and net ammonia production by the cells could be estimated. It became evident that asparagine could support the growth of CHO cells as a stable substitute for glutamine. Then, a glucose fed-batch culture was grown on a glutamine free and asparagine supplemented medium. Because of (1) low glucose concentration, but (2) no glucose limitation and (3) low ammonia accumulation, the maximum total cell concentration reached 3.4 × 106 ml-1, which was 1.8 times greater than that in the control experiment (initial 1.15 g l-1 glucose and 0.29 g l-1 glutamine, and no glucose feed). © 1990.
引用
收藏
页码:113 / 128
页数:16
相关论文
共 25 条
[1]  
Ahlberg J. H., 1967, THEORY SPLINES THEIR
[2]   A MATHEMATICAL MODEL FOR CONTINUOUS CULTURE OF MICROORGANISMS UTILIZING INHIBITORY SUBSTRATES [J].
ANDREWS, JF .
BIOTECHNOLOGY AND BIOENGINEERING, 1968, 10 (06) :707-+
[3]  
Bergmeyer H. U., 1985, METHODS ENZYMATIC AN, V3rd edn., P454
[4]   OPTIMUM FIBER SPACING IN A HOLLOW FIBER BIOREACTOR [J].
CHRESAND, TJ ;
GILLIES, RJ ;
DALE, BE .
BIOTECHNOLOGY AND BIOENGINEERING, 1988, 32 (08) :983-992
[5]  
DAHL RH, 1976, P SOC EXP BIOL MED, V153, P251
[6]   TRANSIENT KINETICS OF HYBRIDOMA GROWTH AND MONOCLONAL-ANTIBODY PRODUCTION IN SERUM-LIMITED CULTURES [J].
DALILI, M ;
OLLIS, DF .
BIOTECHNOLOGY AND BIOENGINEERING, 1989, 33 (08) :984-990
[7]   A NON-LINEAR REGRESSION PROGRAM FOR SMALL COMPUTERS [J].
DUGGLEBY, RG .
ANALYTICAL BIOCHEMISTRY, 1981, 110 (01) :9-18
[8]   CARBOHYDRATE-METABOLISM IN CHINESE-HAMSTER CELLS [J].
FAIK, P ;
MORGAN, MJ .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1976, 4 (06) :1043-1045
[9]   CATABOLIC CONTROL OF MAMMALIAN-CELL CULTURE [J].
GLACKEN, MW .
BIO-TECHNOLOGY, 1988, 6 (09) :1041-&
[10]   REDUCTION OF WASTE PRODUCT EXCRETION VIA NUTRIENT CONTROL - POSSIBLE STRATEGIES FOR MAXIMIZING PRODUCT AND CELL YIELDS ON SERUM IN CULTURES OF MAMMALIAN-CELLS [J].
GLACKEN, MW ;
FLEISCHAKER, RJ ;
SINSKEY, AJ .
BIOTECHNOLOGY AND BIOENGINEERING, 1986, 28 (09) :1376-1389