Metabolic flux analysis in mammalian cell culture

被引:155
作者
Quek, Lake-Ee [1 ]
Dietmair, Stefanie [1 ]
Kroemer, Jens O. [1 ]
Nielsen, Lars K. [1 ]
机构
[1] Univ Queensland, AIBN, Brisbane, Qld 4072, Australia
关键词
Metabolic flux analysis (MFA); Mammalian cells; Review; Constrained-based analysis; Hybridoma; CHO; RECOMBINANT MONOCLONAL-ANTIBODY; MAGNETIC-RESONANCE SPECTROSCOPY; BIOCHEMICAL REACTION SYSTEMS; LINEAR CONSTRAINT RELATIONS; YEAST PYRUVATE-CARBOXYLASE; FED-BATCH CULTURE; HYBRIDOMA CELLS; MYELOMA CELLS; GLUTAMINE-METABOLISM; MASS BALANCES;
D O I
10.1016/j.ymben.2009.09.002
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
Mammalian cell culture metabolism is characterized by glucoglutaminolysis, that is, high glucose and glutamine uptake combined with a high rate of lactate and non-essential amino acid secretion. Stress associated with acid neutralization and ammonia accumulation necessitates complex feeding schemes and limits cell densities achieved in fed-batch culture. Conventional and constraint-based metabolic flux analysis has been successfully used to study the metabolic phenotype of mammalian cells in culture, while C-13 tracer analysis has been used to study small network models and validate assumptions of metabolism. Large-scale C-13 metabolic flux analysis, which is required to improve confidence in the network models and their predictions, remains a major challenge. Advances in both modeling and analytical techniques are bringing this challenge within sight. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:161 / 171
页数:11
相关论文
共 80 条
[1]   Analysis of CHO cells metabolic redistribution in a glutamate-based defined medium in continuous culture [J].
Altamirano, C ;
Illanes, A ;
Casablancas, A ;
Gámez, X ;
Cairó, JJ ;
Gòdia, C .
BIOTECHNOLOGY PROGRESS, 2001, 17 (06) :1032-1041
[2]   Elementary metabolite units (EMU): A novel framework for modeling isotopic distributions [J].
Antoniewicz, Maciek R. ;
Kelleher, Joanne K. ;
Stephanopoulos, Gregory .
METABOLIC ENGINEERING, 2007, 9 (01) :68-86
[3]   Inverse metabolic engineering: A strategy for directed genetic engineering of useful phenotypes [J].
Bailey, JE ;
Sburlati, A ;
Hatzimanikatis, V ;
Lee, K ;
Renner, WA ;
Tsai, PS .
BIOTECHNOLOGY AND BIOENGINEERING, 2002, 79 (05) :568-579
[4]   HIGH-LEVEL EXPRESSION OF A RECOMBINANT ANTIBODY FROM MYELOMA CELLS USING A GLUTAMINE-SYNTHETASE GENE AS AN AMPLIFIABLE SELECTABLE MARKER [J].
BEBBINGTON, CR ;
RENNER, G ;
THOMSON, S ;
KING, D ;
ABRAMS, D ;
YARRANTON, GT .
BIO-TECHNOLOGY, 1992, 10 (02) :169-175
[5]   GENETIC-ENGINEERING OF HYBRIDOMA GLUTAMINE-METABOLISM [J].
BELL, SL ;
BEBBINGTON, C ;
SCOTT, MF ;
WARDELL, JN ;
SPIER, RE ;
BUSHELL, ME ;
SANDERS, PG .
ENZYME AND MICROBIAL TECHNOLOGY, 1995, 17 (02) :98-106
[6]   SELECTING AND DESIGNING CELL-LINES FOR IMPROVED PHYSIOLOGICAL-CHARACTERISTICS [J].
BIRCH, JR ;
BORASTON, RC ;
METCALFE, H ;
BROWN, ME ;
BEBBINGTON, CR ;
FIELD, RP .
CYTOTECHNOLOGY, 1994, 15 (1-3) :11-16
[7]   DETERMINATION OF THE RESPIRATION QUOTIENT IN MAMMALIAN-CELL CULTURE IN BICARBONATE BUFFERED MEDIA [J].
BONARIUS, HPJ ;
DEGOOIJER, CD ;
TRAMPER, J ;
SCHMID, G .
BIOTECHNOLOGY AND BIOENGINEERING, 1995, 45 (06) :524-535
[8]  
Bonarius HPJ, 1998, BIOTECHNOL BIOENG, V58, P258, DOI 10.1002/(SICI)1097-0290(19980420)58:2/3<258::AID-BIT20>3.0.CO
[9]  
2-7
[10]  
Bonarius HPJ, 1996, BIOTECHNOL BIOENG, V50, P299, DOI 10.1002/(SICI)1097-0290(19960505)50:3<299::AID-BIT9>3.0.CO