• Journal of Institute of Control, Robotics and Systems
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• v.11 no.10
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• pp.843-850
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• 2005

FBA(flux balance analysis) with Boolean rules for representing regulatory events has correctly predicted cellular behaviors, such as optimal flux distribution, maximal growth rate, metabolic by-product, and substrate concentration changes, with various environmental conditions. However, until now, since FBA has not taken into account a hierarchical regulatory network, it has limited the representation of the whole transcriptional regulation mechanism and interactions between specific regulatory proteins and genes. In this paper, in order to solve these problems, we describe the construction of hierarchical regulatory network with defined symbols and the introduction of a weight for representing interactions between symbols. Finally, the whole cellular behaviors with time were simulated through the linkage of a hierarchical regulatory network module and dynamic simulation module including FBA. The central metabolic network of E. coli was chosen as the basic model to identify our suggested modeling method.

• KSBB Journal
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• v.22 no.1
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• pp.62-65
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• 2007

New strain development strategy using kinetic models and metabolic control analysis was investigated. In this study, previously reported mathematical models describing the enzyme kinetics of intracellular threonine synthesis were modified for mutant threonine producer Escherichia coli TF5015. Using the modified models, metabolic control analysis was carried out to identify the rate limiting step by evaluating the flux control coefficient on the overall threonine synthesis flux exerted by individual enzymatic reactions. The result suggested the production of threonine could be enhanced most efficiently by increasing aspartate semialdehyde dehydrogenase (asd) activity of this strain. Amplification of asd gene in recombinant strain TF5015 (pCL-$P_{aroF}$-asd) increased the threonine production up to 23%, which is much higher than 14% obtained by amplifying aspartate kinse (thrA), other gene in threonine biosynthesis pathway.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.590-590
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• 2003

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.12-12
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• 2005

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.564-564
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• 2003

• 한국생물공학회:학술대회논문집
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• 2002.04a
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• pp.58-58
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• 2002

• Journal of Microbiology and Biotechnology
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• v.22 no.5
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• pp.659-667
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• 2012

2,3-Butanediol (2,3-BDO) is an organic compound with a wide range of industrial applications. Although Escherichia coli is often used for the production of organic compounds, the wild-type E. coli does not contain two essential genes in the 2,3-BDO biosynthesis pathway, and cannot ferment 2,3-BDO. Therefore, a 2,3-BDO biosynthesis mutant strain of Escherichia coli was constructed and cultured. To determine the optimum culture factors for 2,3-BDO production, experiments were conducted under different culture environments ranging from strongly acidic to neutral pH. The extracellular metabolite profiles were obtained using high-performance liquid chromatography (HPLC), and the intracellular metabolite profiles were analyzed by ultra-performance liquid chromatography and quadruple time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Metabolic flux analysis (MFA) was used to integrate these profiles. The metabolite profiles showed that 2,3-BDO production favors an acidic environment (pH 5), whereas cell mass favors a neutral environment. Furthermore, when the pH of the culture fell below 5, both the cell growth and 2,3-BDO production were inhibited.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2003.10a
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• pp.251-257
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• 2003

Metabolic engineering has become a new paradigm for the more efficient production of desired bioproducts. Metabolic engineering can be defined as directed modification of cellular metabolism and properties through the introduction, deletion, and modification of metabolic pathways by using recombinant DNA and other molecular biological tools. During the last decade, metabolic flux analysis(MFA) has become an essential tool fur metabolic engineering. By MFA, the intracellular metabolic fluxes can be quantified by the measurement of extracellular metabolite concentrations in combination with the stoichiometry of intracellular reactions and mass balances. The usefulness and functionality of MFA are demonstrated by applying to metabolic pathways in E. coli. First, a large-scale in silico E. coli model is constructed, and then the effects of carbon sources on intracellular flux distributions and succinic acid production were investigated on the basis of the uptake and secretion rates of the relevant metabolites. The results indicated that succinic acid yields increased in order of gluconate, glucose and sorbitol. Acetic acid and lactic acid were produced as major products rather than when gluconate and glucose were used carbon sources. The results indicated that among three carbon sources available, the most reduced substrate is sorbitol which yields efficient succinic acid production.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.793-794
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• 2005

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.632-633
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• 2005