A Protocol for Lab-Scale Production of ¹³C-Labeled Yeast Extract as Internal Standard for Metabolomics and Quantification of Intracellular Metabolites.
- 1Department of Biotechnology, Delft University of Technology, Delft, the Netherlands.
- 2These authors contributed equally to this work.
Abstract
Metabolomics enables the profiling of small-molecule metabolites, thereby capturing the biochemical state of a living organism at a given moment and making it possible to monitor the organism's cellular responses to stimuli. This technique has become a powerful tool in pharmaceutical research, the food industry, and microbial research. Metabolomics aims to obtain an unbiased metabolic profile; however, this is complicated by compound instability, the requirement for complex and often extensive sample processing, and nonlinear responses in mass spectrometry. Therefore, correcting for metabolite loss and mass-spectrometry-related artifacts is essential; this is typically achieved through relative quantification against an isotopically labeled internal standard for each metabolite of interest. This article describes a method to produce ¹³C-labeled yeast extract and its use as internal standard for metabolomics. More specifically, it provides step-by-step protocols for the fed-batch fermentation, quenching, metabolite extraction, and LC-MS and GC-MS characterization of the internal standard. It also includes a protocol explaining how to use the internal standard for the quantification of metabolites in yeast samples. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Trial run-fed-batch fermentation Support Protocol 1: Dry weight determination Basic Protocol 2: Quenching and washing of the cell samples and metabolite extraction Basic Protocol 3: Identification of intracellular metabolites using LC-MS Basic Protocol 4: Identification of intracellular metabolites using GC-MS Basic Protocol 5: Real run-fed-batch fermentation Basic Protocol 6: LC-MS characterization of the internal standard Basic Protocol 7: GC-MS characterization of the internal standard Basic Protocol 8: Quantification of metabolites in yeast samples.
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BibTeX
@article{cammaert2026protocol,
title = {{A Protocol for Lab-Scale Production of ¹³C-Labeled Yeast Extract as Internal Standard for Metabolomics and Quantification of Intracellular Metabolites.}},
author = {Miriam Cammaert and Rosalie Wouters and Jitske van Ede and Erik de Hulster and Christiaan Mooiman and Patricia van Dam and Martin Pabst and Walter van Gulik and Pascale Daran-Lapujade},
journal = {Current protocols},
year = {2026},
month = nov,
doi = {10.1002/cpz1.70470},
url = {https://europepmc.org/article/MED/42975294},
note = {CC BY},
}
RIS
TY - JOUR
TI - A Protocol for Lab-Scale Production of ¹³C-Labeled Yeast Extract as Internal Standard for Metabolomics and Quantification of Intracellular Metabolites.
AU - Miriam Cammaert
AU - Rosalie Wouters
AU - Jitske van Ede
AU - Erik de Hulster
AU - Christiaan Mooiman
AU - Patricia van Dam
AU - Martin Pabst
AU - Walter van Gulik
AU - Pascale Daran-Lapujade
PY - 2026
DA - 2026/11/01
JO - Current protocols
DO - 10.1002/cpz1.70470
UR - https://europepmc.org/article/MED/42975294
AB - Metabolomics enables the profiling of small-molecule metabolites, thereby capturing the biochemical state of a living organism at a given moment and making it possible to monitor the organism's cellular responses to stimuli. This technique has become a powerful tool in pharmaceutical research, the food industry, and microbial research. Metabolomics aims to obtain an unbiased metabolic profile; however, this is complicated by compound instability, the requirement for complex and often extensive sample processing, and nonlinear responses in mass spectrometry. Therefore, correcting for metabolite loss and mass-spectrometry-related artifacts is essential; this is typically achieved through relative quantification against an isotopically labeled internal standard for each metabolite of interest. This article describes a method to produce ¹³C-labeled yeast extract and its use as internal standard for metabolomics. More specifically, it provides step-by-step protocols for the fed-batch fermentation, quenching, metabolite extraction, and LC-MS and GC-MS characterization of the internal standard. It also includes a protocol explaining how to use the internal standard for the quantification of metabolites in yeast samples. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Trial run-fed-batch fermentation Support Protocol 1: Dry weight determination Basic Protocol 2: Quenching and washing of the cell samples and metabolite extraction Basic Protocol 3: Identification of intracellular metabolites using LC-MS Basic Protocol 4: Identification of intracellular metabolites using GC-MS Basic Protocol 5: Real run-fed-batch fermentation Basic Protocol 6: LC-MS characterization of the internal standard Basic Protocol 7: GC-MS characterization of the internal standard Basic Protocol 8: Quantification of metabolites in yeast samples.
SN - 2691-1299
ER -