• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.5
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• pp.237-251
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• 2002

The recent progress on metabolic systems engineering was reviewed based on our recent research results in terms of (1) metabolic signal flow diagram approach, (2) metabolic flux analysis (MFA) in particular with intracellular isotopomer distribution using NMR and/or GC-MS, (3) synthesis and optimization of metabolic flux distribution (MFD), (4) modification of MFD by gene manipulation and by controlling culture environment, (5) metabolic control analysis (MCA), (6) design of metabolic regulation structure, and (7) identification of unknown pathways with isotope tracing by NMR. The main characteristics of metabolic engineering is to treat metabolism as a network or entirety instead of individual reactions. The applications were made for poly-3-hydroxybutyrate (PHB) production using Ralstonia eutropha and recombinant Escherichia coli, lactate production by recombinant Saccharomyces cerevisiae, pyruvate production by vitamin auxotrophic yeast Toluropsis glabrata, lysine production using Corynebacterium glutamicum, and energetic analysis of photosynthesic microorganisms such as Cyanobateria. The characteristics of each approach were reviewed with their applications. The approach based on isotope labeling experiments gives reliable and quantitative results for metabolic flux analysis. It should be recognized that the next stage should be toward the investigation of metabolic flux analysis with gene and protein expressions to uncover the metabolic regulation in relation to genetic modification and/ or the change in the culture condition.

• Journal of Institute of Control, Robotics and Systems
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• v.11 no.10
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• pp.823-829
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• 2005

We have newly constructed an in silico model of fermentative metabolism for Lactococcus lactis in order to analyze the characteristics of metabolite flux for dynamic network. A rigorous mathematical model for metabolic flux has been developed and simulation researches have been performed by using GEPASI program. In this simulation task, we were able to predict the whole flux distribution trend for lactate metabolism and analyze the flux ratio on the pyruvate branch point by using metabolic flux analysis(MFA). And we have studied flux control coefficients of key reaction steps in the model by using metabolic control analysis(MCA). The role of pyruvate branch seems to be essential for the secretion of lactate and other organic byproducts. Then we have made an effort to elucidate its metabolic regulation characteristics and key reaction steps, and find an optimal condition for the production of lactate.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1916-1927
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• 2018

Corynebacterium glutamicum is an excellent platform for the production of amino acids, and is widely used in the fermentation industry. Most industrial strains are traditionally obtained by repeated processes of random mutation and selection, but the genotype of these strains is often unclear owing to the absence of genomic information. As such, it is difficult to improve the growth and amino acid production of these strains via metabolic engineering. In this study, we generated a complete genome map of an industrial L-valine-producing strain, C. glutamicum XV. In order to establish the relationship between genotypes and physiological characteristics, a comparative genomic analysis was performed to explore the core genome, structural variations, and gene mutations referring to an industrial L-leucine-producing strain, C. glutamicum CP, and the widely used C. glutamicum ATCC 13032. The results indicate that a 36,349 bp repeat sequence in the CP genome contained an additional copy each of lrp and brnFE genes, which benefited the export of L-leucine. However, in XV, the kgd and panB genes were disrupted by nucleotide insertion, which increase the availability of precursors to synthesize L-valine. Moreover, the specific amino acid substitutions in key enzymes increased their activities. Additionally, a novel strategy is proposed to remodel central carbon metabolism and reduce pyruvate consumption without having a negative impact on cell growth by introducing the CP-derived mutant $H^+$/citrate symporter. These results further our understanding regarding the metabolic networks in these strains and help to elucidate the influence of different genotypes on these processes.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.5
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• pp.462-469
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• 2005

A top-down approach is known to be a useful and effective technique for the design and analysis of metabolic systems. In this Study, we have constructed a grouped metabolic network for Lactococcus lactis under aerobic conditions using grouped enzyme kinetics. To test the usefulness of grouping work, a non-grouped system and grouped systems were compared quantitatively with each other. Here, grouped Systems were designed as two groups according to the extent of grouping. The overall simulated flux values in grouped and non-grouped models had pretty similar distribution trends, but the details on flux ratio at the pyruvate branch point showed a little difference. This result indicates that our grouping technique can be used as a good model for complicated metabolic networks, however, for detailed analysis of metabolic network, a more robust mechanism Should be considered. In addition to the data for the pyruvate branch point analysis, Some major flux control coefficients were obtained in this research.

• Research in Community and Public Health Nursing
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• v.30 no.3
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• pp.271-280
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• 2019

Purpose: This study evaluates the efficacy of a Self-Care Reinforcement Program (SCRP) based on the Selection Optimization Compensation (SOC) model, in socially vulnerable elderly women with metabolic syndrome. Methods: This study adopts a pretest-posttest nonequivalent control group design. The participants were 64 socially vulnerable elderly Korean women with metabolic syndrome (experimental group: 31, control group: 33). Participants' body composition analysis, nutrient intake, risk factors of metabolic syndrome, depressive symptoms, and social network were measured. Data were analyzed with an independent t-test; statistical significance levels were set at p<.05. The SCRP, including metabolic syndrome education, nutritional education, exercise, and social network, was performed three times a week for 8 weeks. Results: There were statistically significant differences between the experimental and control groups in terms of systolic blood pressure, diastolic pressure, fasting blood sugar, triglycerides, sodium intake, depressive symptoms, and social networks. Conclusion: The SCRP is effective and can be recommended as a community health nursing intervention for socially vulnerable elderly women with metabolic syndrome.

• Journal of Microbiology and Biotechnology
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• v.21 no.2
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• pp.162-169
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• 2011

A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.61-62
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• 2001

• Research in Community and Public Health Nursing
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• v.26 no.2
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• pp.128-139
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• 2015

Purpose: The purpose of this study was to identify factors affecting health promotion behavior among workers with high risk of metabolic syndrome. This study was based on the planned behavior theory. Methods: The participants were 167 workers at high risk of metabolic syndrome. Data were collected using a structured questionnaire. Surveyed variables were attitude, subjective norm, perceived behavioral control, intention, and health promotion behavior. Data were analyzed using descriptive statistics, t-test, ANOVA, Pearson's correlation coefficients, and hierarchical regression analysis with SPSS/WIN 22.0. Results: Perceived behavioral control affected the intention of health promotion behavior among the workers with high risk of metabolic syndrome. It explained 62% of variance in the intention of health promotion behavior (F=40.09, p<.001). Perceived behavioral control and occupation affected health promotion behavior among the risk workers with high risk of metabolic syndrome. The two factors explained 16% of variance in health promotion behavior (F=4.95, p<.001). Conclusion: The findings of this study suggest that perceived behavioral control is the only factor affecting health promotion behavior when the theory of planned behavior was applied. Therefore, intervention programs for improving health promotion behavior should be focused on strengthening perceived behavioral control.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.175-175
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• 2017

To understand molecular mechanisms underlying adaptation of plant cells to saline stress and stress memory, we developed Arabidopsis callus suspension-cultured cells adapted to high salt. Adapted cells to high salt exhibited enhanced tolerance compared to control cells. Moreover, the salt tolerance of adapted cells was stably maintained even after the stress is relieved, indicating that the acquired salt tolerance of adapted cells was memorized. In order to characterize metabolic responses of plant cells during adaptation to high salt stress as well as stress memory, we compared metabolic profiles of salt-adapted and stress-memorized cells with control cells by using NMR spectroscopy. A principle component analysis showed clear metabolic discrimination among control, salt-adapted and stress-memorized cells. Compared with control cells, metabolites related to shikimate metabolism such as tyrosine, and flavonol glycosides, which are related to protective mechanism of plant against stresses were largely up-regulated in adapted cell lines. Moreover, coniferin, a precursor of lignin, was more abundant in salt-adapted cells than control cells. Cell morphology analysis using transmission electron microscopy indicated that cell wall thickness of salt-adapted cells was significantly induced compared to control cells. Consistently, salt adapted cells contained more lignin in their cell walls compared to control cells. The results provide new insight into mechanisms of plant adaptation to saline stress as well as stress memory in metabolic level.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.13-16
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• 2000

Microorganisms have been widely employed for the production of useful bioproducts including primary metabolites such as ethanol, succinic acid, acetone and butanol, secondary metabolites represented by antibiotics, proteins, polysaccharides, lipids and many others. Since these products can be obtained in small quantities under natural condition, mutation and selection processes have been employed for the improvement of strains. Recently, metabolic engineering strategies have been employed for more efficient production of these bioproducts. Metabolic engineering can be defined as purposeful modification of cellular metabolic pathways by introducing new pathways, deleting or modifying the existing pathways for the enhanced production of a desired product or modified/new product, degradation of xenobiotics, and utilization of inexpensive raw materials. Metabolic flux analysis and metabolic control analysis along with recombinant DNA techniques are three important components in designing optimized metabolic pathways, This powerful technology is being further improved by the genomics, proteomics, metabolomics and bioinformatics. Complete genome sequences are providing us with the possibility of addressing complex biological questions including metabolic control, regulation and flux. In silico analysis of microbial metabolic pathways is possible from the completed genome sequences. Transcriptome analysis by employing ONA chip allows us to examine the global pattern of gene expression at mRNA level. Two dimensional gel electrophoresis of cellular proteins can be used to examine the global proteome content, which provides us with the information on gene expression at protein level. Bioinformatics can help us to understand the results obtained with these new techniques, and further provides us with a wide range of information contained in the genome sequences. The strategies taken in our lab for the production of pharmaceutical proteins, polyhydroxyalkanoate (a family of completely biodegradable polymer), succinic acid and me chemicals by employing metabolic engineering powered by genomics, proteomics, metabolomics and bioinformatics will be presented.