Novel strategy for non-targeted isotope-assisted metabolomics by means of metabolic turnover and multivariate analysis

Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic net...

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Published inMetabolites Vol. 4; no. 3; pp. 722 - 739
Main Authors Nakayama, Yasumune, Tamada, Yoshihiro, Tsugawa, Hiroshi, Bamba, Takeshi, Fukusaki, Eiichiro
Format Journal Article
LanguageEnglish
Published Switzerland MDPI 25.08.2014
MDPI AG
Subjects
gas chromatography
isotope-assisted metabolomics
mass spectrometry
metabolic turnover analysis
metabolomics
non-targeted analysis
Saccharomyces cerevisiae
stable isotope
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Abstract Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch points of metabolic pathways, and assignment of elemental formulas to unknown metabolites. Furthermore, some data processing tools have been developed to apply these techniques to a non-targeted approach, which plays an important role in revealing unknown or unexpected metabolism. However, data collection and integration strategies for non-targeted isotope-assisted metabolomics have not been established. Therefore, a systematic approach is proposed to elucidate metabolic dynamics without targeting pathways by means of time-resolved isotope tracking, i.e., "metabolic turnover analysis", as well as multivariate analysis. We applied this approach to study the metabolic dynamics in amino acid perturbation of Saccharomyces cerevisiae. In metabolic turnover analysis, 69 peaks including 35 unidentified peaks were investigated. Multivariate analysis of metabolic turnover successfully detected a pathway known to be inhibited by amino acid perturbation. In addition, our strategy enabled identification of unknown peaks putatively related to the perturbation.
AbstractList Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch points of metabolic pathways, and assignment of elemental formulas to unknown metabolites. Furthermore, some data processing tools have been developed to apply these techniques to a non-targeted approach, which plays an important role in revealing unknown or unexpected metabolism. However, data collection and integration strategies for non-targeted isotope-assisted metabolomics have not been established. Therefore, a systematic approach is proposed to elucidate metabolic dynamics without targeting pathways by means of time-resolved isotope tracking, i.e., “metabolic turnover analysis”, as well as multivariate analysis. We applied this approach to study the metabolic dynamics in amino acid perturbation of Saccharomyces cerevisiae. In metabolic turnover analysis, 69 peaks including 35 unidentified peaks were investigated. Multivariate analysis of metabolic turnover successfully detected a pathway known to be inhibited by amino acid perturbation. In addition, our strategy enabled identification of unknown peaks putatively related to the perturbation.
Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch points of metabolic pathways, and assignment of elemental formulas to unknown metabolites. Furthermore, some data processing tools have been developed to apply these techniques to a non-targeted approach, which plays an important role in revealing unknown or unexpected metabolism. However, data collection and integration strategies for non-targeted isotope-assisted metabolomics have not been established. Therefore, a systematic approach is proposed to elucidate metabolic dynamics without targeting pathways by means of time-resolved isotope tracking, i.e. , “metabolic turnover analysis”, as well as multivariate analysis. We applied this approach to study the metabolic dynamics in amino acid perturbation of Saccharomyces cerevisiae . In metabolic turnover analysis, 69 peaks including 35 unidentified peaks were investigated. Multivariate analysis of metabolic turnover successfully detected a pathway known to be inhibited by amino acid perturbation. In addition, our strategy enabled identification of unknown peaks putatively related to the perturbation.
Author Bamba, Takeshi
Nakayama, Yasumune
Fukusaki, Eiichiro
Tsugawa, Hiroshi
Tamada, Yoshihiro
AuthorAffiliation 2 RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
1 Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan; E-Mails: yasumune_nakayama@bio.eng.osaka-u.ac.jp (Y.N.); yoshihiro-tamada@hakutsuru.co.jp (Y.T.); hiroshi.tsugawa@riken.jp (H.T.); bamba@bio.eng.osaka-u.ac.jp (T.B.)
AuthorAffiliation_xml – name: 2 RIKEN Center for Sustainable Resource Science, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
– name: 1 Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan; E-Mails: yasumune_nakayama@bio.eng.osaka-u.ac.jp (Y.N.); yoshihiro-tamada@hakutsuru.co.jp (Y.T.); hiroshi.tsugawa@riken.jp (H.T.); bamba@bio.eng.osaka-u.ac.jp (T.B.)
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/25257997$$D View this record in MEDLINE/PubMed
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    fullname: Nakahigashi
– ident: ref23
  doi: 10.1186/1471-2105-12-131
– volume: 1
  start-page: 1
  year: 1999
  ident: ref13
  article-title: Metabolic fluxes and metabolic engineering
  publication-title: Metab. Eng.
  doi: 10.1006/mben.1998.0101
  contributor:
    fullname: Stephanopoulos
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Snippet Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted...
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SubjectTerms gas chromatography
isotope-assisted metabolomics
mass spectrometry
metabolic turnover analysis
metabolomics
non-targeted analysis
Saccharomyces cerevisiae
stable isotope
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Title Novel strategy for non-targeted isotope-assisted metabolomics by means of metabolic turnover and multivariate analysis
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