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Special Issue "Microbial Metabolomics"

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A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Microbiology and Ecological Metabolomics".

Deadline for manuscript submissions: closed (20 September 2013) | Viewed by 42397

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Dr. Walter M. Van Gulik
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Guest Editor

Department of Biotechnology, Kluyver Centre for Genomics of Industrial Fermentation, Delft University of Technology, Delft, The Netherlands
Interests: microbial fermentation; metabolic modeling; metabolomics; systems biology

Special Issue Information

Dear Colleagues,

During the last decade significant progress has been made in the field of quantitative as well as stable isotope based microbial metabolomics, not only with respect to the optimization and validation of sampling, quenching and sample processing methods, but also the improvement of MS based analytics, data processing and mathematical modelling. Next to a further increase of the portfolio of small molecules to be quantified and improvement of the sensitivity and selectivity, is the application of metabolomics to answer intriguing biological questions. Apart from aiming at obtaining a better understanding of the physiology and metabolic regulation of microorganisms in general, these could be focused on the heterogeneity of individuals in clonal populations, cell cycle processes, cell to cell communication, the role of the individual members of microbial communities, compartmentation of metabolic pathways in eukaryotic microbes, solute transport across cellular membranes and so on. This might require the quantification of metabolites in individual cellular compartments and/or in individual cells, which are still big challenges.
This special issue of Metabolites will be dedicated not only to the development of new and the improvement of existing microbial metabolomics techniques, but also to the application of these techniques to tackle intriguing biological questions, thereby integrating metabolomics with other omics data and applying modelling approaches to gain insight in the overwhelming diversity of microbial metabolism, both from a fundamental as well as an applied point of view.

Dr. Walter M. van Gulik
Guest Editor

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Keywords

quantitative metabolomics
stable isotopes
data processing
data integration
metabolic modelling
compartmentation
membrane transport
metabolic regulation
cell cycle
heterogeneity
microbial communities

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Microbial Metabolomics Volume 2 in Metabolites (4 articles)

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Research

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Open AccessArticle

Quantitative Metabolomics and Instationary ¹³C-Metabolic Flux Analysis Reveals Impact of Recombinant Protein Production on Trehalose and Energy Metabolism in Pichia pastoris

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Metabolites 2014, 4(2), 281-299; https://doi.org/10.3390/metabo4020281 - 05 May 2014

Cited by 27 | Viewed by 8154

Abstract

Pichia pastoris has been recognized as an effective host for recombinant protein production. In this work, we combine metabolomics and instationary ¹³C metabolic flux analysis (INST ¹³C-MFA) using GC-MS and LC-MS/MS to evaluate the potential impact of the production of a Rhizopus oryzae lipase (Rol) on P. pastoris central carbon metabolism. Higher oxygen uptake and CO₂ production rates and slightly reduced biomass yield suggest an increased energy demand for the producing strain. This observation is further confirmed by ¹³C-based metabolic flux analysis. In particular, the flux through the methanol oxidation pathway and the TCA cycle was increased in the Rol-producing strain compared to the reference strain. Next to changes in the flux distribution, significant variations in intracellular metabolite concentrations were observed. Most notably, the pools of trehalose, which is related to cellular stress response, and xylose, which is linked to methanol assimilation, were significantly increased in the recombinant strain. Full article

(This article belongs to the Special Issue Microbial Metabolomics)

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Open AccessArticle

Cellulose Digestion and Metabolism Induced Biocatalytic Transitions in Anaerobic Microbial Ecosystems

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Metabolites 2014, 4(1), 36-52; https://doi.org/10.3390/metabo4010036 - 31 Dec 2013

Cited by 19 | Viewed by 8262

Abstract

Anaerobic digestion of highly polymerized biomass by microbial communities present in diverse microbial ecosystems is an indispensable metabolic process for biogeochemical cycling in nature and for industrial activities required to maintain a sustainable society. Therefore, the evaluation of the complicated microbial metabolomics presents a significant challenge. We here describe a comprehensive strategy for characterizing the degradation of highly crystallized bacterial cellulose (BC) that is accompanied by metabolite production for identifying the responsible biocatalysts, including microorganisms and their metabolic functions. To this end, we employed two-dimensional solid- and one-dimensional solution-state nuclear magnetic resonance (NMR) profiling combined with a metagenomic approach using stable isotope labeling. The key components of biocatalytic reactions determined using a metagenomic approach were correlated with cellulose degradation and metabolic products. The results indicate that BC degradation was mediated by cellulases that contain carbohydrate-binding modules and that belong to structural type A. The degradation reactions induced the metabolic dynamics of the microbial community and produced organic compounds, such as acetic acid and propionic acid, mainly metabolized by clostridial species. This combinatorial, functional and structural metagenomic approach is useful for the comprehensive characterization of biomass degradation, metabolic dynamics and their key components in diverse ecosystems. Full article

(This article belongs to the Special Issue Microbial Metabolomics)

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Open AccessArticle

Metabolomic Analysis of Fission Yeast at the Onset of Nitrogen Starvation

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Metabolites 2013, 3(4), 1118-1129; https://doi.org/10.3390/metabo3041118 - 13 Dec 2013

Cited by 26 | Viewed by 8915

Abstract

Microorganisms naturally respond to changes in nutritional conditions by adjusting their morphology and physiology. The cellular response of the fission yeast S. pombe to nitrogen starvation has been extensively studied. Here, we report time course metabolomic analysis during one hour immediately after nitrogen starvation, prior to any visible changes in cell morphology except for a tiny increase of cell length per division cycle. We semi-quantitatively measured 75 distinct metabolites, 60% of which changed their level over 2-fold. The most significant changes occurred during the first 15 min, when trehalose, 2-oxoglutarate, and succinate increased, while purine biosynthesis intermediates rapidly diminished. At 30–60 min, free amino acids decreased, although several modified amino acids—including hercynylcysteine sulfoxide, a precursor to ergothioneine—accumulated. Most high-energy metabolites such as ATP, S-adenosyl-methionine or NAD⁺ remained stable during the whole time course. Very rapid metabolic changes such as the shut-off of purine biosynthesis and the rise of 2-oxoglutarate and succinate can be explained by the depletion of NH₄Cl. The changes in the levels of key metabolites, particularly 2-oxoglutarate, might represent an important mechanistic step to trigger subsequent cellular regulations. Full article

(This article belongs to the Special Issue Microbial Metabolomics)

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Open AccessArticle

Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae

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Metabolites 2013, 3(4), 1102-1117; https://doi.org/10.3390/metabo3041102 - 06 Dec 2013

Cited by 9 | Viewed by 7745

Abstract

Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP) and aqueous normal phase (ANP) chromatographic separations, as well as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources for detection in both ion polarities. Unsupervised principle component analysis (PCA) and ANOVA results revealed differentiation between wild-type controls, calcium stressed and immunosuppressant/calcium challenged cells. Untargeted data mining resulted in 247 differentially expressed, annotated metabolites, across at least one pair of conditions. A separate, targeted data mining strategy identified 187 differential, annotated metabolites. All annotated metabolites were subsequently mapped onto curated pathways from YeastCyc and WikiPathways for interactive pathway analysis and visualization. Dozens of pathways showed differential responses to stress conditions based on one or more matches to the list of annotated metabolites or to metabolites that had been identified further by MS/MS. The purine salvage, pantothenate and sulfur amino acid pathways were flagged as being enriched, which is consistent with previously published literature for transcriptomics analysis. Thus, broad discovery-based data mining combined with targeted pathway projections can be an important asset for rapidly distilling, testing and evaluating a large amount of information for further investigation. Full article

(This article belongs to the Special Issue Microbial Metabolomics)

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Review

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Open AccessReview

Metabolomics for Secondary Metabolite Research

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Metabolites 2013, 3(4), 1076-1083; https://doi.org/10.3390/metabo3041076 - 11 Nov 2013

Cited by 30 | Viewed by 8884

Abstract

Metabolomics, the global characterization of metabolite profiles, is becoming an increasingly powerful tool for research on secondary metabolite discovery and production. In this review we discuss examples of recent technological advances and biological applications of metabolomics in the search for chemical novelty and [...] Read more.

(This article belongs to the Special Issue Microbial Metabolomics)

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