13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media

Saccharomyces cerevisiae is often cultivated in complex media for applications in food and other biochemical production. However, 13C-metabolic flux analysis (13C-MFA) has been conducted for S. cerevisiae cultivated in synthetic media, resulting in a limited understanding of the metabolic flux distr...

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Main Authors: Hayato Fujiwara, Nobuyuki Okahashi, Taisuke Seike, Fumio Matsuda
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Metabolic Engineering Communications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214030125000045
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author Hayato Fujiwara
Nobuyuki Okahashi
Taisuke Seike
Fumio Matsuda
author_facet Hayato Fujiwara
Nobuyuki Okahashi
Taisuke Seike
Fumio Matsuda
author_sort Hayato Fujiwara
collection DOAJ
description Saccharomyces cerevisiae is often cultivated in complex media for applications in food and other biochemical production. However, 13C-metabolic flux analysis (13C-MFA) has been conducted for S. cerevisiae cultivated in synthetic media, resulting in a limited understanding of the metabolic flux distributions under the complex media. In this study, 13C-MFA was applied to S. cerevisiae cultivated in complex media to quantify the metabolic fluxes in the central metabolic network. S. cerevisiae was cultivated in a synthetic dextrose (SD) medium supplemented with 20 amino acids (SD + AA) and yeast extract peptone dextrose (YPD) medium. The results revealed that glutamic acid, glutamine, aspartic acid, and asparagine are incorporated into the TCA cycle as carbon sources in parallel with glucose consumption. Based on these findings, we successfully conducted 13C-MFA of S. cerevisiae cultivated in SD + AA and YPD media using parallel labeling and measured amino acid uptake rates. Furthermore, we applied the developed approach to 13C-MFA of yeast cultivated in malt extract medium. The analysis revealed that the metabolic flux through the anaplerotic and oxidative pentose phosphate pathways was lower in complex media than in synthetic media. Owing to the reduced carbon loss by the branching pathways, carbon flow toward ethanol production via glycolysis could be elevated. 13C-MFA of S. cerevisiae cultured in complex media provides valuable insights for metabolic engineering and process optimization in industrial yeast fermentation.
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spelling doaj-art-f2bcff81984e4c68a12a3b95500e2f4b2025-08-20T03:31:11ZengElsevierMetabolic Engineering Communications2214-03012025-06-0120e0026010.1016/j.mec.2025.e0026013C-metabolic flux analysis of Saccharomyces cerevisiae in complex mediaHayato Fujiwara0Nobuyuki Okahashi1Taisuke Seike2Fumio Matsuda3Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan; Osaka University Shimadzu Omics Innovation Research Laboratories, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Industrial Biotechnology Initiative Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan; Osaka University Shimadzu Omics Innovation Research Laboratories, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Industrial Biotechnology Initiative Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Corresponding author. Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.Saccharomyces cerevisiae is often cultivated in complex media for applications in food and other biochemical production. However, 13C-metabolic flux analysis (13C-MFA) has been conducted for S. cerevisiae cultivated in synthetic media, resulting in a limited understanding of the metabolic flux distributions under the complex media. In this study, 13C-MFA was applied to S. cerevisiae cultivated in complex media to quantify the metabolic fluxes in the central metabolic network. S. cerevisiae was cultivated in a synthetic dextrose (SD) medium supplemented with 20 amino acids (SD + AA) and yeast extract peptone dextrose (YPD) medium. The results revealed that glutamic acid, glutamine, aspartic acid, and asparagine are incorporated into the TCA cycle as carbon sources in parallel with glucose consumption. Based on these findings, we successfully conducted 13C-MFA of S. cerevisiae cultivated in SD + AA and YPD media using parallel labeling and measured amino acid uptake rates. Furthermore, we applied the developed approach to 13C-MFA of yeast cultivated in malt extract medium. The analysis revealed that the metabolic flux through the anaplerotic and oxidative pentose phosphate pathways was lower in complex media than in synthetic media. Owing to the reduced carbon loss by the branching pathways, carbon flow toward ethanol production via glycolysis could be elevated. 13C-MFA of S. cerevisiae cultured in complex media provides valuable insights for metabolic engineering and process optimization in industrial yeast fermentation.http://www.sciencedirect.com/science/article/pii/S221403012500004513C-based metabolic flux analysisCentral carbon metabolismSaccharomyces cerevisiaeComplex media
spellingShingle Hayato Fujiwara
Nobuyuki Okahashi
Taisuke Seike
Fumio Matsuda
13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media
Metabolic Engineering Communications
13C-based metabolic flux analysis
Central carbon metabolism
Saccharomyces cerevisiae
Complex media
title 13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media
title_full 13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media
title_fullStr 13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media
title_full_unstemmed 13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media
title_short 13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media
title_sort 13c metabolic flux analysis of saccharomyces cerevisiae in complex media
topic 13C-based metabolic flux analysis
Central carbon metabolism
Saccharomyces cerevisiae
Complex media
url http://www.sciencedirect.com/science/article/pii/S2214030125000045
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