Biotechnology Letters

, Volume 29, Issue 1, pp 1–16

Microbial metabolomics: past, present and future methodologies

  • Mlawule R. Mashego
  • Karl Rumbold
  • Marjan De Mey
  • Erick Vandamme
  • Wim Soetaert
  • Joseph J. Heijnen


Microbial metabolomics has received much attention in recent years mainly because it supports and complements a wide range of microbial research areas from new drug discovery efforts to metabolic engineering. Broadly, the term metabolomics refers to the comprehensive (qualitative and quantitative) analysis of the complete set of all low molecular weight metabolites present in and around growing cells at a given time during their growth or production cycle. This review focuses on the past, current and future development of various experimental protocols in the rapid developing area of metabolomics in the ongoing quest to reliably quantify microbial metabolites formed under defined physiological conditions. These developments range from rapid sample collection, instant quenching of microbial metabolic activity, extraction of the relevant intracellular metabolites as well as quantification of these metabolites using enzyme based and or modern high tech hyphenated analytical protocols, mainly chromatographic techniques coupled to mass spectrometry (LC-MSn, GC-MSn, CE-MSn), where n indicates the number of tandem mass spectrometry, and nuclear magnetic resonance spectroscopy (NMR).


Bacteria Chromatography Filamentous fungi Mass spectrometry Metabolomics Metabolite extraction Quenching Rapid sampling Yeast 



Quantification of the total metabolites complement inside and outside a cell under defined growth conditions


Total metabolites excreted outside the cell (culture supernatant)


Total metabolites located inside the cell (Intracellularly)


Qualitative analysis of exometabolome


Qualitative analysis of endometabolome

Target analysis

Quantitative analysis of known pre-defined metabolites concentrations


Instantaneous arrest of endogenous metabolic activity


Gas chromatography coupled to mass spectrometry


Liquid chromatography coupled to electrospray ionisation mass spectrometry


uattro Time of light


Fourier transform-ion cyclotron resonance


Capillary electrophoresis coupled to mass spectrometry

Metabolite turnover rate

The inverse of the metabolite pool size to metabolite flux ratio


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© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Mlawule R. Mashego
    • 1
    • 2
  • Karl Rumbold
    • 2
  • Marjan De Mey
    • 2
  • Erick Vandamme
    • 2
  • Wim Soetaert
    • 2
  • Joseph J. Heijnen
    • 1
  1. 1.Department of Biotechnology, Faculty of Applied SciencesTechnical University of DelftDelftThe Netherlands
  2. 2.Department of Biochemical and Microbial Technology, Laboratory of Industrial Microbiology and Biocatalysis, Faculty of Bioscience EngineeringGhent UniversityGentBelgium

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