Journal
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
Volume 118, Issue 3, Pages 350-355Publisher
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2014.02.014
Keywords
Dynamic analysis of metabolic pathway; Metabolomics; TCA cycle; Saccharomyces cerevisiae; Yeast; Stable isotope; Fumarate respiration; C-13-glucose; Principal component analysis
Funding
- JST
- Strategic International Collaborative Research Program (JST-SICORP)
- JSTCREST
- Grants-in-Aid for Scientific Research [23686120] Funding Source: KAKEN
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Visualization of metabolic dynamism is important for various types of metabolic studies including studies on optimization of bio-production processes and studies of metabolism-related diseases. Many methodologies have been developed for metabolic studies. Among these, metabolic turnover analysis (MTA) is often used to analyze metabolic dynamics. MTA involves observation of changes in the isotopomer ratio of metabolites over time following introduction of isotope-labeled substrates. MTA has several advantages compared with C-13-metabolic flux analysis, including the diversity of applicable samples, the variety of isotope tracers, and the wide range of target pathways. However, MTA produces highly complex data from which mining useful information becomes difficult. For easy understanding of MTA data, a new approach was developed using principal component analysis (PCA). The resulting PCA score plot visualizes the metabolic distance, which is defined as distance between metabolites on the real metabolic map. And the score plot gives us some hints of interesting metabolism for further study. We used this method to analyze the central metabolism of Saccharomyces cerevisiae under moderated aerobic conditions, and time course data for 77 isotopomers of 14 metabolites were obtained. The PCA score plot for this dataset represented a metabolic map and indicated interesting phenomena such as activity of fumarate reductase under aerated condition. These findings show the importance of a multivariate analysis to MTA. In addition, because the approach is not biased, this method has potential application for analysis of less-studied pathways and organisms. (c) 2014, The Society for Biotechnology, Japan. All rights reserved.
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