Reconstruction and analysis of a genome-scale metabolic network of Corynebacterium glutamicum S9114

Mei, Jie; Xu, Nan; Ye, Chao; Liu, Li; Wu, Jianrong

doi:10.1016/j.gene.2015.09.038

Cited by 29 publications

(15 citation statements)

References 57 publications

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“…27), the Gram-positive bacterium Corynebacterium glutamicum (iJM658; ref. 28), the filamentous fungus Aspergillus niger 29 and the cyanobacterium Synechocystis sp. PCC 6803 (ref.…”

mentioning

confidence: 99%

Growth-coupled overproduction is feasible for almost all metabolites in five major production organisms

2017

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Computational modelling of metabolic networks has become an established procedure in the metabolic engineering of production strains. One key principle that is frequently used to guide the rational design of microbial cell factories is the stoichiometric coupling of growth and product synthesis, which makes production of the desired compound obligatory for growth. Here we show that the coupling of growth and production is feasible under appropriate conditions for almost all metabolites in genome-scale metabolic models of five major production organisms. These organisms comprise eukaryotes and prokaryotes as well as heterotrophic and photoautotrophic organisms, which shows that growth coupling as a strain design principle has a wide applicability. The feasibility of coupling is proven by calculating appropriate reaction knockouts, which enforce the coupling behaviour. The study presented here is the most comprehensive computational investigation of growth-coupled production so far and its results are of fundamental importance for rational metabolic engineering.

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“…27), the Gram-positive bacterium Corynebacterium glutamicum (iJM658; ref. 28), the filamentous fungus Aspergillus niger 29 and the cyanobacterium Synechocystis sp. PCC 6803 (ref.…”

mentioning

confidence: 99%

Growth-coupled overproduction is feasible for almost all metabolites in five major production organisms

2017

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“…Further, the carbapenemases produced by natural environmental bacteria and Archaea significantly contribute to selection of new mutations. Soil bacterial species greatly influences our life; therefore, a genome-scale metabolic network [53] has proved to be a valid approach to evaluate the complex dynamics of soil bacterial species, mostly in geographic areas near huge hospitals with many departments. Also, innate resistance to antibiotics has raised over time a growing interest for a rational design of new antibacterial compounds [54].…”

Section: Final Remarksmentioning

confidence: 99%

The Emerging Problems of Carbapenem-Resistant Gram- Negative Bacillary Pneumonia

Ionescu¹

2017

Contemporary Topics of Pneumonia

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Carbapenem-resistant Gram-negative organisms are increasingly isolated from lower respiratory tract infections. Limited treatment options are the main problems for physicians and clinical microbiologists who have to face such clinical cases. Bacteriological diagnosis, starting with accurate Gram smear performed from properly collected specimens and ending with antibiotic susceptibility testing, is essential. Morphological characters of bacterial cells provide important clues about the nature of infection, prior to bacterial isolation and identification. Attempts to find complementary options for the respiratory contamination and treatment of carbapenem-resistant Gram-negative bacillary pneumonia led us to test the susceptibility of 21 essential oils. Among them, Thymus vulgaris, Eugenia caryophyllata, Origanum vulgare, Melaleuca alternifolia and Aniba rosaeodora essential oils proved to be efficient against Acinetobacter baumannii carbapenem-resistant strain and Escherichia coli ATCC 25922. In an attempt to evaluate the magnitude of environmental spreading of the carbapenemase genes, 40 carbapenemase sequences of different organisms were compared. Carbapenemases show striking similarities inside each beta-lactamase class (A, D, and B), no matter their originenvironmental organisms or clinical isolates. Class B carbapenemases are most widely distributed, metallo-beta-lactamases being present in bacteria as well in Archaea.

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“…The imbalance of the mass and charge in a few reactions (e.g., synthesis of RNA, protein, and biomass) and the directionality of certain reactions without thermodynamic constraints had a negative effect on genome-wide prediction using the two models. Moreover, the two models have incomplete l -glutamate metabolic systems, which prevented their application in studies of the metabolic state of l -glutamate production in the stationary phase [22, 27]. In 2016, Mei et al constructed i JM658 based on the genome information of C. glutamicum S9114, which was generated by mutagenesis and is widely used for industrial l -glutamate production [27].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the two models have incomplete l -glutamate metabolic systems, which prevented their application in studies of the metabolic state of l -glutamate production in the stationary phase [22, 27]. In 2016, Mei et al constructed i JM658 based on the genome information of C. glutamicum S9114, which was generated by mutagenesis and is widely used for industrial l -glutamate production [27]. i JM658 contains l -glutamate secretion and uptake systems, which could be more suitable for studying l -glutamate production [27].…”

Section: Introductionmentioning

confidence: 99%

“…In 2016, Mei et al constructed i JM658 based on the genome information of C. glutamicum S9114, which was generated by mutagenesis and is widely used for industrial l -glutamate production [27]. i JM658 contains l -glutamate secretion and uptake systems, which could be more suitable for studying l -glutamate production [27]. i JM658 is not applicable for the prediction of metabolic profile of C. glutamicum ATCC13032 due to the presence of numerous differences in the genome sequences between C. glutamicum S9114 and ATCC13032.…”

Section: Introductionmentioning

confidence: 99%

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A new genome-scale metabolic model of Corynebacterium glutamicum and its application

Zhang

Cai

Shang

et al. 2017

Biotechnol Biofuels

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Background Corynebacterium glutamicum is an important platform organism for industrial biotechnology to produce amino acids, organic acids, bioplastic monomers, and biofuels. The metabolic flexibility, broad substrate spectrum, and fermentative robustness of C. glutamicum make this organism an ideal cell factory to manufacture desired products. With increases in gene function, transport system, and metabolic profile information under certain conditions, developing a comprehensive genome-scale metabolic model (GEM) of C. glutamicum ATCC13032 is desired to improve prediction accuracy, elucidate cellular metabolism, and guide metabolic engineering.ResultsHere, we constructed a new GEM for ATCC13032, iCW773, consisting of 773 genes, 950 metabolites, and 1207 reactions. Compared to the previous model, iCW773 supplemented 496 gene–protein-reaction associations, refined five lumped reactions, balanced the mass and charge, and constrained the directionality of reactions. The simulated growth rates of C. glutamicum cultivated on seven different carbon sources using iCW773 were consistent with experimental values. Pearson’s correlation coefficient between the iCW773-simulated and experimental fluxes was 0.99, suggesting that iCW773 provided an accurate intracellular flux distribution of the wild-type strain growing on glucose. Furthermore, genetic interventions for overproducing l-lysine, 1,2-propanediol and isobutanol simulated using OptForceMUST were in accordance with reported experimental results, indicating the practicability of iCW773 for the design of metabolic networks to overproduce desired products. In vivo genetic modifications of iCW773-predicted targets resulted in the de novo generation of an l-proline-overproducing strain. In fed-batch culture, the engineered C. glutamicum strain produced 66.43 g/L l-proline in 60 h with a yield of 0.26 g/g (l-proline/glucose) and a productivity of 1.11 g/L/h. To our knowledge, this is the highest titer and productivity reported for l-proline production using glucose as the carbon resource in a minimal medium.ConclusionsOur developed iCW773 serves as a high-quality platform for model-guided strain design to produce industrial bioproducts of interest. This new GEM will be a successful multidisciplinary tool and will make valuable contributions to metabolic engineering in academia and industry.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-017-0856-3) contains supplementary material, which is available to authorized users.

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Reconstruction and analysis of a genome-scale metabolic network of Corynebacterium glutamicum S9114

Cited by 29 publications

References 57 publications

Growth-coupled overproduction is feasible for almost all metabolites in five major production organisms

Growth-coupled overproduction is feasible for almost all metabolites in five major production organisms

The Emerging Problems of Carbapenem-Resistant Gram- Negative Bacillary Pneumonia

A new genome-scale metabolic model of Corynebacterium glutamicum and its application

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