Special Issue "Microbial Metabolomics"

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A special issue of Metabolites (ISSN 2218-1989).

Deadline for manuscript submissions: closed (20 September 2013)

Special Issue Editor

Guest Editor
Dr. Walter M. van Gulik

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

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charges (APC) is waived for well prepared manuscripts in 2012 and starting January 2013, the APC is 300 CHF per accepted paper. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

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

Published Papers (5 papers)

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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
Metabolites 2014, 4(2), 281-299; doi:10.3390/metabo4020281
Received: 26 February 2014 / Revised: 8 April 2014 / Accepted: 23 April 2014 / Published: 5 May 2014
Cited by 6 | PDF Full-text (498 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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)
Open AccessArticle Cellulose Digestion and Metabolism Induced Biocatalytic Transitions in Anaerobic Microbial Ecosystems
Metabolites 2014, 4(1), 36-52; doi:10.3390/metabo4010036
Received: 13 September 2013 / Revised: 18 December 2013 / Accepted: 20 December 2013 / Published: 31 December 2013
Cited by 7 | PDF Full-text (935 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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
Metabolites 2013, 3(4), 1118-1129; doi:10.3390/metabo3041118
Received: 8 November 2013 / Revised: 3 December 2013 / Accepted: 6 December 2013 / Published: 13 December 2013
Cited by 6 | PDF Full-text (1069 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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)
Open AccessArticle Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae
Metabolites 2013, 3(4), 1102-1117; doi:10.3390/metabo3041102
Received: 15 October 2013 / Revised: 20 November 2013 / Accepted: 25 November 2013 / Published: 6 December 2013
Cited by 4 | PDF Full-text (992 KB) | HTML Full-text | XML Full-text | Supplementary Files
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 [...] Read more.
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
Metabolites 2013, 3(4), 1076-1083; doi:10.3390/metabo3041076
Received: 24 September 2013 / Revised: 25 October 2013 / Accepted: 1 November 2013 / Published: 11 November 2013
Cited by 7 | PDF Full-text (153 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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 the engineered production of bioactive secondary metabolites. Full article
(This article belongs to the Special Issue Microbial Metabolomics)
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