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Applications of Metabolic Modeling to Drive Bioprocess Development for the Production of Value-added Chemicals

  • Mahadevan, Radhakrishnan;Burgard, Anthony P.;Famili, Iman;Dien, Steve Van;Schilling, Christophe H.
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.5
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    • pp.408-417
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    • 2005
  • Increasing numbers of value added chemicals are being produced using microbial fermentation strategies. Computational modeling and simulation of microbial metabolism is rapidly becoming an enabling technology that is driving a new paradigm to accelerate the bioprocess development cycle. In particular, constraint-based modeling and the development of genome-scale models of industrial microbes are finding increasing utility across many phases of the bioprocess development workflow. Herein, we review and discuss the requirements and trends in the industrial application of this technology as we build toward integrated computational/experimental platforms for bioprocess engineering. Specifically we cover the following topics: (1) genome-scale models as genetically and biochemically consistent representations of metabolic networks; (2) the ability of these models to predict, assess, and interpret metabolic physiology and flux states of metabolism; (3) the model-guided integrative analysis of high throughput 'omics' data; (4) the reconciliation and analysis of on- and off-line fermentation data as well as flux tracing data; (5) model-aided strain design strategies and the integration of calculated biotransformation routes; and (6) control and optimization of the fermentation processes. Collectively, constraint-based modeling strategies are impacting the iterative characterization of metabolic flux states throughout the bioprocess development cycle, while also driving metabolic engineering strategies and fermentation optimization.

Common MCL1 polymorphisms associated with risk of tuberculosis

  • Shin, Hyoung-Doo;Cheong, Hyun-Sub;Park, Byung-Lae;Kim, Lyoung-Hyo;Han, Chang-Su;Lee, In-Hee;Park, Seung-Kyu
    • BMB Reports
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    • v.41 no.4
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    • pp.334-337
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    • 2008
  • MCL1 expression has been found to be up-regulated during infection with virulent Mycobacterium tuberculosis. We investigated the genetic polymorphisms in MCL1 as potential candidate gene for a host genetic study of clinical TB infection. We have sequenced exons and their boundaries of MCL1, including the 1.5 kb promoter region, to identify polymorphisms, and eight polymorphisms were identified. The genetic associations of polymorphisms in MCL1 with clinical TB patients (n=486) and normal controls (n=370) were analyzed. Using statistical analyses, one common promoter polymorphism (MCL1-324C>A) which is absolutely linked with three other SNPs in the promoter and 3'UTR regions, were found to be significantly associated with increased risk of clinical TB disease. The frequency of the A-bearing genotype of -324C>A was higher in clinical TB patients than in normal controls (P=0.0008, OR=1.68). Our findings suggest that polymorphisms in MCL1 might be one of genetic factors for the risk of clinical tuberculosis development.

Stability of Recombinant Plasmids Carrying the stb Locus of E. coli IncFII NR1 Plasmid in E. coli and Yeast (대장균과 효모에서 Escherichia coli IncFII NR1 플라스미드의 stb 좌위를 포함하는 재조합 플라스미드의 안정성에 관한 연구)

  • Chung, Kung-Sook;Kim, Choon-Kwang;Kim, Kyu-Won
    • Korean Journal of Microbiology
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    • v.31 no.1
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    • pp.37-43
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    • 1993
  • The effect of stb locus of E. COLI IncFII plasmid NR1 on the stability of chimeric plasmids was investigated. First, we have isolated the stability locus (stb) from E. coli NR1 plasmid and then inserted into the three different vectors, pUC8, YRp17 and YEp24. By examining their stability in E. coli and yeast, we showed that the recombinant plasmids containing stb locus were resonably stable. Also, by comparing the amounts of the rDNA fragments per haploid genome with those of the plasmid fragments, we showed they copy number of recombinant plasmids was not increased. Consequently, the stb locus of E. coli IncFII plasmid NR1 stabilized the chimeric plasmids but did not affect the replication or copy number of plasmids.

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A Study on the Removal of LPP CMP Induced Defect (LPP(Landing Plug Poly) CMP Induced Defect 제거에 관한 연구)

  • Oh, Pyeong-Won;Choi, Jea-Gon;Choi, Yong-Soo;Choi, Geun-Min;Song, Yong-Wook
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2004.07a
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    • pp.235-238
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    • 2004
  • 본 연구는 반도체소자 제조공정에 적용되는 CMP공정 중 LPP(Landing Plug Poly) Contact간의 소자 분리를 위해 진행되는 LPP CMP의 후 세정 과정에서 유발되는 방사형 Defect 제거에 관한 내용이다. 방사형 Defect은 LPP CMP 후에 노출되는 BPSG, Poly, Nitride Film과 연마재로 사용되는SiO2 입자, 후 세정과정에서 적용되는 SC-1, DHF, $NH_4OH$ Chemical과 Brush와의 상호작용에 의해 발생되며, Cleaning시의 산성 분위기 하에서 각 물질간의 pH와 Zeta Potential의 차이에서 기인한다. 이 Defect을 제거하기 위해 LPP CMP후에 Film 표면에 노출되는 각 물질의 표면 특성과 CMP 후 오염입자의 흡착과 재 흡착에 영향을 미치는 Electrostatic force와 Van der Waals force, PVA Brush에 의한 Mechanical force의 상호작용을 고려하여 최적 후 세정 조건을 제시 하였다.

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