Metabolomics in Metabolic Engineering

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

Deadline for manuscript submissions: closed (15 October 2012) | Viewed by 26949

Special Issue Editor


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Guest Editor
Institute for Bioscience and Biotechnology Research (IBBR), Fischell Department of Bioengineering, University of Maryland, 9600 Gudelsky Drive, Room A231, Rockville, MD 20850, USA
Interests: biodesign and biological engineering; plant synthetic biology; protein design and engineering; gene-metabolite relationships in medicinal plants; protein expression and production

Special Issue Information

Dear Colleagues,

Stunning advances in synthetic biology have enabled plants and microorganisms to be engineered for the increased production of a wide variety of useful and important metabolites.  These breakthroughs have benefited from computational, experimental and technical developments, especially in the areas of genomics and systems biology, and include transcriptomics and metabolomics, as well as modeling efforts to integrate global data on a cellular level.  Improved tools for biodesign are increasing our ability to rapidly identify, manipulate and regulate metabolic pathways.  Not only are metabolic engineering efforts enhancing our understanding of how interconnected cellular networks can contribute to and affect metabolism and cellular control, but they are finding broad application to pharmaceutical development, nutritional enhancement of plants to improve human health, biomanufacturing and biofuel production.  Accordingly, a special issue of Metabolites will focus on multidisciplinary aspects to the design and engineering of diverse biosystems for the production of endogenous or novel metabolites, and highlight computational, experimental or technical approaches for metabolic engineering.

Dr. Edward Eisenstein
Guest Editor

Keywords

  • metabolomics
  • metabolic engineering
  • systems biology
  • biodesign
  • secondary metabolites
  • natural products
  • biomanufacturing
  • nutrition
  • biofuel

Published Papers (3 papers)

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Research

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679 KiB  
Article
Changes in Primary and Secondary Metabolite Levels in Response to Gene Targeting-Mediated Site-Directed Mutagenesis of the Anthranilate Synthase Gene in Rice
by Hiroaki Saika, Akira Oikawa, Ryo Nakabayashi, Fumio Matsuda, Kazuki Saito and Seiichi Toki
Metabolites 2012, 2(4), 1123-1138; https://doi.org/10.3390/metabo2041123 - 18 Dec 2012
Cited by 8 | Viewed by 7886
Abstract
Gene targeting (GT) via homologous recombination allows precise modification of a target gene of interest. In a previous study, we successfully used GT to produce rice plants accumulating high levels of free tryptophan (Trp) in mature seeds and young leaves via targeted modification [...] Read more.
Gene targeting (GT) via homologous recombination allows precise modification of a target gene of interest. In a previous study, we successfully used GT to produce rice plants accumulating high levels of free tryptophan (Trp) in mature seeds and young leaves via targeted modification of a gene encoding anthranilate synthase—a key enzyme of Trp biosynthesis. Here, we performed metabolome analysis in the leaves and mature seeds of GT plants. Of 72 metabolites detected in both organs, a total of 13, including Trp, involved in amino acid metabolism, accumulated to levels >1.5-fold higher than controls in both leaves and mature seeds of GT plants. Surprisingly, the contents of certain metabolites valuable for both humans and livestock, such as γ-aminobutyric acid and vitamin B, were significantly increased in mature seeds of GT plants. Moreover, untargeted analysis using LC-MS revealed that secondary metabolites, including an indole alkaloid, 2-[2-hydroxy-3-β-d-glucopyranosyloxy-1-(1H-indol-3-yl)propyl] tryptophan, also accumulate to higher levels in GT plants. Some of these metabolite changes in plants produced via GT are similar to those observed in plants over expressing mutated genes, thus demonstrating that in vivo protein engineering via GT can be an effective approach to metabolic engineering in crops. Full article
(This article belongs to the Special Issue Metabolomics in Metabolic Engineering)
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Review

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604 KiB  
Review
Exometabolomics Approaches in Studying the Application of Lignocellulosic Biomass as Fermentation Feedstock
by Ying Zha and Peter J. Punt
Metabolites 2013, 3(1), 119-143; https://doi.org/10.3390/metabo3010119 - 11 Feb 2013
Cited by 10 | Viewed by 8280
Abstract
Lignocellulosic biomass is the future feedstock for the production of biofuel and bio-based chemicals. The pretreatment-hydrolysis product of biomass, so-called hydrolysate, contains not only fermentable sugars, but also compounds that inhibit its fermentability by microbes. To reduce the toxicity of hydrolysates as fermentation [...] Read more.
Lignocellulosic biomass is the future feedstock for the production of biofuel and bio-based chemicals. The pretreatment-hydrolysis product of biomass, so-called hydrolysate, contains not only fermentable sugars, but also compounds that inhibit its fermentability by microbes. To reduce the toxicity of hydrolysates as fermentation media, knowledge of the identity of inhibitors and their dynamics in hydrolysates need to be obtained. In the past decade, various studies have applied targeted metabolomics approaches to examine the composition of biomass hydrolysates. In these studies, analytical methods like HPLC, RP-HPLC, CE, GC-MS and LC-MS/MS were used to detect and quantify small carboxylic acids, furans and phenols. Through applying targeted metabolomics approaches, inhibitors were identified in hydrolysates and their dynamics in fermentation processes were monitored. However, to reveal the overall composition of different hydrolysates and to investigate its influence on hydrolysate fermentation performance, a non-targeted metabolomics study needs to be conducted. In this review, a non-targeted and generic metabolomics approach is introduced to explore inhibitor identification in biomass hydrolysates, and other similar metabolomics questions. Full article
(This article belongs to the Special Issue Metabolomics in Metabolic Engineering)
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338 KiB  
Review
Systematic Applications of Metabolomics in Metabolic Engineering
by Robert A. Dromms and Mark P. Styczynski
Metabolites 2012, 2(4), 1090-1122; https://doi.org/10.3390/metabo2041090 - 14 Dec 2012
Cited by 17 | Viewed by 10064
Abstract
The goals of metabolic engineering are well-served by the biological information provided by metabolomics: information on how the cell is currently using its biochemical resources is perhaps one of the best ways to inform strategies to engineer a cell to produce a target [...] Read more.
The goals of metabolic engineering are well-served by the biological information provided by metabolomics: information on how the cell is currently using its biochemical resources is perhaps one of the best ways to inform strategies to engineer a cell to produce a target compound. Using the analysis of extracellular or intracellular levels of the target compound (or a few closely related molecules) to drive metabolic engineering is quite common. However, there is surprisingly little systematic use of metabolomics datasets, which simultaneously measure hundreds of metabolites rather than just a few, for that same purpose. Here, we review the most common systematic approaches to integrating metabolite data with metabolic engineering, with emphasis on existing efforts to use whole-metabolome datasets. We then review some of the most common approaches for computational modeling of cell-wide metabolism, including constraint-based models, and discuss current computational approaches that explicitly use metabolomics data. We conclude with discussion of the broader potential of computational approaches that systematically use metabolomics data to drive metabolic engineering. Full article
(This article belongs to the Special Issue Metabolomics in Metabolic Engineering)
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