A small metabolic flux model to identify transient metabolic regulations in Saccharomyces cerevisiae

被引:33
作者
Herwig, C [1 ]
von Stockar, U [1 ]
机构
[1] Swiss Fed Inst Technol, EPFL, Lab Chem & Biochem Engn, CH-1015 Lausanne, Switzerland
关键词
D O I
10.1007/s00449-001-0277-2
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
The understanding of dynamic metabolic regulations is important for physiological studies and strain characterization tasks. The present study combined transient experiments with online metabolic flux analysis (MFA) in order to quantify metabolic regulations, namely carbon catabolite repression of respiration and transient acetic-acid production, in Saccharomyces cerevisiae during aerobic growth on glucose. The aim was to investigate which additional information can be gained from using a small metabolic flux model to study transient growth provoked by shift-up and shift-down experiments, compared to online monitoring alone. The MFA model allowed us to propose new correlations between pathways of the central metabolism. A linear correlation between glycolytic flux and respiratory capacity holds for shift-down and shift-up experiments. This confirmed that respiratory functions were subjected to carbon catabolite repression and suggested that respiratory capacity is controlled by the glycolytic flux rather than the glucose influx. Furthermore, the model showed that control of repression of respiration by the glycolytic flux was a dynamic phenomenon. Co-factor balancing within the MFA model showed that transient acetic-acid production indicated a transient limitation in another part of the central metabolism but not in oxidative phosphorylation. However, at super-critical growth rates and when coupling of anabolism and catabolism is resumed, the limitation shifts to oxidative phosphorylation, with the consequence that ethanol is formed. The online application of small metabolic flux models to transient experiments enhanced the physiological insight into transient growth and opens up the use of transient experiments as an efficient tool to understand dynamic metabolic regulations.
引用
收藏
页码:395 / 403
页数:9
相关论文
共 37 条
[1]   Distributed control of the glycolytic flux in wild-type cells and catabolite repression mutants of Saccharomyces cerevisiae growing in carbon-limited chemostat cultures [J].
Cortassa, S ;
Aon, MA .
ENZYME AND MICROBIAL TECHNOLOGY, 1997, 21 (08) :596-602
[2]  
Duboc P, 1998, BIOTECHNOL BIOENG, V60, P180, DOI 10.1002/(SICI)1097-0290(19981020)60:2<180::AID-BIT5>3.0.CO
[3]  
2-J
[4]  
Duboc P, 1998, BIOTECHNOL BIOENG, V57, P610, DOI 10.1002/(SICI)1097-0290(19980305)57:5<610::AID-BIT13>3.0.CO
[5]  
2-F
[6]   REGULATION OF GLUCOSE-METABOLISM IN GROWING YEAST-CELLS [J].
FIECHTER, A ;
FUHRMANN, GF ;
KAPPELI, O .
ADVANCES IN MICROBIAL PHYSIOLOGY, 1981, 22 :123-183
[7]   Metabolic responses of pyruvate decarboxylase-negative Saccharomyces cerevisiae to glucose excess [J].
Flikweert, MT ;
vanDijken, JP ;
Pronk, JT .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 1997, 63 (09) :3399-3404
[8]  
Flikweert MT, 1999, BIOTECHNOL BIOENG, V66, P42, DOI [10.1002/(SICI)1097-0290(1999)66:1<42::AID-BIT4>3.0.CO
[9]  
2-L, 10.1002/(SICI)1097-0290(1999)66:1&lt
[10]  
42::AID-BIT4&gt