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1.
Chinese Journal of Biotechnology ; (12): 1526-1540, 2021.
Article in Chinese | WPRIM | ID: wpr-878653

ABSTRACT

Genome-scale metabolic network model (GSMM) is becoming an important tool for studying cellular metabolic characteristics, and remarkable advances in relevant theories and methods have been made. Recently, various constraint-based GSMMs that integrated genomic, transcriptomic, proteomic, and thermodynamic data have been developed. These developments, together with the theoretical breakthroughs, have greatly contributed to identification of target genes, systems metabolic engineering, drug discovery, understanding disease mechanism, and many others. This review summarizes how to incorporate transcriptomic, proteomic, and thermodynamic-constraints into GSMM, and illustrates the shortcomings and challenges of applying each of these methods. Finally, we illustrate how to develop and refine a fully integrated GSMM by incorporating transcriptomic, proteomic, and thermodynamic constraints, and discuss future perspectives of constraint-based GSMM.


Subject(s)
Genome/genetics , Metabolic Engineering , Metabolic Networks and Pathways/genetics , Models, Biological , Proteomics
2.
Chinese Journal of Biotechnology ; (12): 860-873, 2021.
Article in Chinese | WPRIM | ID: wpr-878601

ABSTRACT

Genome-scale metabolic network model (GSMM) is an extremely important guiding tool in the targeted modification of industrial microbial strains, which helps researchers to quickly obtain industrial microbes with specific traits and has attracted increasing attention. Here we reviewe the development history of GSMM and summarized the construction method of GSMM. Furthermore, the development and application of GSMM in industrial microorganisms are elaborated by using four typical industrial microorganisms (Bacillus subtilis, Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae) as examples. In addition, prospects in the development trend of GSMM are proposed.


Subject(s)
Corynebacterium glutamicum/genetics , Escherichia coli/genetics , Metabolic Engineering , Metabolic Networks and Pathways/genetics
3.
Braz. arch. biol. technol ; 64: e21190480, 2021. tab, graf
Article in English | LILACS | ID: biblio-1278442

ABSTRACT

Abstract The evolution of species is inevitably accompanied by the evolution of metabolic networks to adapt to different environments. The metabolic networks of different species were collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website, and some enzyme reactions with the highest occurrence frequency in all species were found and are reported in this paper. The correlation coefficients of whether the enzyme reactions appear in all species were calculated, and the corresponding evolutionary correlation connection networks were calculated according to different correlation coefficient thresholds. These studies show that, as the evolutionary correlation of enzyme reactions increases, the weighted average of the mean functional concentration ratios of the enzyme reactions also increases, indicating that the functional concentration ratio of enzyme reactions has a certain correlation with the evolutionary correlation. The work presented in this paper enhances our understanding of the characteristics and general rules of metabolic network evolution.


Subject(s)
Enzyme Activation , Metabolic Networks and Pathways , Adaptation, Biological , Metabolism
4.
Chinese Journal of Biotechnology ; (12): 1914-1924, 2019.
Article in Chinese | WPRIM | ID: wpr-771743

ABSTRACT

Genome-scale metabolic network models have been successfully applied to guide metabolic engineering. However, the conventional flux balance analysis only considers stoichiometry and reaction direction constraints, and the simulation results cannot accurately describe certain phenomena such as overflow metabolism and diauxie growth on two substrates. Recently, researchers proposed new constraint-based methods to simulate the cellular behavior under different conditions more precisely by introducing new constraints such as limited enzyme content and thermodynamics feasibility. Here we review several enzyme-constrained models, giving a comprehensive introduction on the biological basis and mathematical representation for the enzyme constraint, the optimization function, the impact on the calculated flux distribution and their application in identification of metabolic engineering targets. The main problems in these existing methods and the perspectives on this emerging research field are also discussed. By introducing new constraints, metabolic network models can simulate and predict cellular behavior under various environmental and genetic perturbations more accurately, and thus can provide more reliable guidance to strain engineering.


Subject(s)
Enzymes , Metabolism , Genome , Genetics , Metabolic Engineering , Metabolic Networks and Pathways , Genetics , Models, Biological , Thermodynamics
5.
Braz. arch. biol. technol ; 62: e19180071, 2019. tab, graf
Article in English | LILACS | ID: biblio-1055371

ABSTRACT

Abstract 13C metabolic flux analysis (13C-MFA) has achieved increasing significance in quantitative metabolic system analysis in recent years. In 13C metabolic flux analysis, 13C-FLUX software is a major analytical tool. The software's input script is primarily expressed in textual form without visual presentation of the structure of the entire metabolic network, thus error-prone in manual input. To solve this problem, we have developed a visual FTBL generator (VFG, available at http://47.100.98.220/vfg/index.jsp in a Google or Firefox browser)for MFA that eliminates the tedious, error-prone text entry mode and provides a user-friendly graphical interface and simple visual reaction generation functions.


Subject(s)
Database , Metabolic Networks and Pathways , Metabolic Flux Analysis , Data Visualization
6.
Article in Chinese | WPRIM | ID: wpr-607168

ABSTRACT

Objective To investigate the gender differences of glucose metabolic network in brains of healthy adults at resting state by 18F-FDG PET.Methods A total of 204 dextromanual,healthy individuals (104 males,average age:(53.45±11.51) years;100 females,average age:(54.11±12.09) years) were enrolled from June 2011 to June 2016 to construct brain metabolic networks.The nodal and global parameters,including clustering coefficient (Cp),characteristic path length (Lp) and betweenness centrality (Cb),were analyzed by graph theory.Permutation test with 1 000 repetitions was used.Results The brain metabolic networks derived from 18F-FDG PET data were with small-world properties in both male group and female group.Compared with Cb in females,Cb in males was significantly reduced in left postcentral gyrus,right angular gyrus and left temporal pole/middle temporal gyrus (permutation test,all P0.05).Conclusions There are gender-related differences of topological structure in whole-brain metabolic networks.Gender should be considered as a covariate while designing experiments,accounting for cerebral metabolic data from normal control and experimental patients as well as making clinical decisions.

7.
Braz. arch. biol. technol ; 59: e16150429, 2016. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-951303

ABSTRACT

Metabolic network alignments enable comparison of the similarities and differences between pathways in two metabolic networks and help to uncover the conserved sub-blocks therein. Such analysis is important in the understanding of metabolic networks and species evolution. The fundamental parts of metabolic network alignment algorithms all involve comparisons of the similarity between two enzymes as a similarity measure of network nodes. As a result, the study of methods for measuring enzyme similarity becomes highly relevant. Currently, two approaches are mainly used to measure enzyme similarity. One of the methods is based on similarity measures of gene or protein sequences; the other is based on enzyme classification. In this study, multiple metabolic network alignments were performed using both the methods. The results showed that, in general, the sequence similarity method yielded higher accuracy, especially with respect to reflecting evolutionary distances.

8.
Chinese Journal of Biotechnology ; (12): 1010-1025, 2016.
Article in Chinese | WPRIM | ID: wpr-242278

ABSTRACT

Aspergillus niger, as an important industrial fermentation strain, is widely applied in the production of organic acids and industrial enzymes. With the development of diverse omics technologies, the data of genome, transcriptome, proteome and metabolome of A. niger are increasing continuously, which declared the coming era of big data for the research in fermentation process of A. niger. The data analysis from single omics and the comparison of multi-omics, to the integrations of multi-omics based on the genome-scale metabolic network model largely extends the intensive and systematic understanding of the efficient production mechanism of A. niger. It also provides possibilities for the reasonable global optimization of strain performance by genetic modification and process regulation. We reviewed and summarized progress in omics research of A. niger, and proposed the development direction of omics research on this cell factory.


Subject(s)
Aspergillus niger , Genetics , Fermentation , Genome, Fungal , Metabolic Networks and Pathways , Metabolome , Proteome , Transcriptome
9.
Article in Chinese | WPRIM | ID: wpr-854471

ABSTRACT

The anti-depressive effect of Xiaoyaosan is obvious; However, the potential mechanism remains unclear. This paper elucidated the antidepressive mechanism of Xiaoyaosan from the fields of neurotransmitter, neurotrophins, hypothalamic-pituitary- adrenal axis, metabolisms of amino acid, lipid, and energy, inflammatory factor, and metabolic network figure. The comprehensive results implicate that Xiaoyaosan plays as antidepressant via the role of action on multiple targets and regulation in the metabolic balance in vivo.

10.
Article in Chinese | WPRIM | ID: wpr-438659

ABSTRACT

This study was aimed to build metabolic network of hypertension with syndrome of ascendant hyper-activity of liver yang by associating metabolic biomarkers in order to reveal the biological nature of hyperten-sion from the whole view . According to the diagnostic criteria of hypertension with syndrome of ascendant hy-peractivity of liver yang, typical cases were selected and healthy volunteers were enrolled as comparison . Metabolic biomarkers were revealed by metabolomics methods. The metabolic pathways of biomarkers were re-vealed with the KEGG database . The metabolic pathways were connected to establish the metabolic network . Key targets were identified using metabolism node analysis . The results showed that compared with healthy vol-unteers , the metabolic network of hypertension with syndrome of ascendant hyperactivity of liver yang had sig-nificant changes . Norepinephrine , hexanose and arachidonic acid are key network nodes . It was concluded that the metabolic network according to metabolic biomarkers has the advantage in the study on changes of the body under complicated conditions . The study provided a scientific basis for the understanding of biological na-ture of hypertension with syndrome of ascendant hyperactivity of liver yang.

11.
Braz. j. microbiol ; 40(2): 411-416, Apr.-June 2009. ilus, graf, tab
Article in English | LILACS | ID: lil-520231

ABSTRACT

The purpose of this work was to study the giant strong component (GSC) of B. thuringiensis metabolic network by structural and functional analysis. Based on so-called "bow tie" structure, we extracted and studied GSC with its functional significance. Global structural properties such as degree distribution and average path length were computed and indicated that the GSC is also a small-world and scale-free network. Furthermore, the GSC was decomposed and functional significant for metabolism of these divisions were investigated by comparing to KEGG metabolic pathways.


O objetivo deste trabalho foi realizar uma análise estrutural e funcional do GSC (Giant Strong Component) da rede metabólica de Bacillus thurigiensis. Baseando-se na estrutura bow-tie, o GSC foi extraído e analisado quanto ao sue significado funcional. Propriedades estruturais globais tais como grau de distribuição e tamanho médio da via metabólica foram mensuradas, concluindo-se que o GSC é também uma rede small world e scalefree. Além disso, a rede GSC foi decomposta e as divisões com significância funcional no metabolismo foram comparadas às vias metabólicas KEGG.


Subject(s)
Bacillus thuringiensis/metabolism , Metabolism , Methods , Methods
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