• 제목/요약/키워드: metabolic pathway

검색결과 503건 처리시간 0.026초

Prediction of Maximum Yields of Metabolites and Optimal Pathways for Their Production by Metabolic Flux Analysis

  • Hong, Soon-Ho;Moon, Soo-Yun;Lee, Sang-Yup
    • Journal of Microbiology and Biotechnology
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    • 제13권4호
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    • pp.571-577
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    • 2003
  • The intracellular metabolic fluxes can be calculated by metabolic flux analysis, which uses a stoichiometric model for the intracellulal reactions along with mass balances around the intracellular metabolites. In this study, metabolic flux analyses were carried out to estimate flux distributions for the maximum in silico yields of various metabolites in Escherichia coli. The maximum in silico yields of acetic acid and lactic acid were identical to their theoretical yields. On the other hand, the in silico yields of succinic acid and ethanol were only 83% and 6.5% of their theoretical yields, respectively. The lower in silico yield of succinic acid was found to be due to the insufficient reducing power. but this lower yield could be increased to its theoretical yield by supplying more reducing power. The maximum theoretical yield of ethanol could be achieved, when a reaction catalyzed by pyruvate decarboxylase was added in the metabolic network. Futhermore, optimal metabolic pathways for the production of various metabolites could be proposed, based on the results of metabolic flux analyses. In the case of succinic acid production, it was found that the pyruvate carboxylation pathway should be used for its optimal production in E. coli rather than the phosphoenolpyruvate carboxylation pathway.

The Pentose Phosphate Pathway as a Potential Target for Cancer Therapy

  • Cho, Eunae Sandra;Cha, Yong Hoon;Kim, Hyun Sil;Kim, Nam Hee;Yook, Jong In
    • Biomolecules & Therapeutics
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    • 제26권1호
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    • pp.29-38
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    • 2018
  • During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

구조적 특징에 기반한 대사 경로 드로잉 알고리즘 (An Algorithm for Drawing Metabolic Pathways based on Structural Characteristics)

  • 이소희;송은하;이상호;박현석
    • 한국정보과학회논문지:소프트웨어및응용
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    • 제31권10호
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    • pp.1266-1275
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    • 2004
  • '생물정보학'이란 생물학적 데이타를 처리, 가공하여 정보를 얻어내는 연구 분야로 이 중 대사 체학은 대사 경로 네트워크를 가시화하여 생명 활동을 이해하고자 하는 분야로, 대사 경로 내의 흐름을 한 눈에 알 수 있도록 가시화하여 보여 줄 수 있는 도구가 반드시 필요하다. 따라서 본 논문에서는 새로운 '대사 경로 드로잉 알고리즘'을 제안하였다. 대사 경로 그래프의 구조로는 이분 그래프를 이용하여 가독성을 높였으며, 이 그래프가 척도 없는(scale-free) 네트워크 구조라는 것과 구조적으로 환형, 계층적, 선형 컴포넌트를 가진다는 것을 고려하여 사이즈가 큰 그래프도 적절하게 드로잉 하도록 하였다.

식물에서 Carotenoid 생합성 경로와 대사공학적 응용 (Carotenoids Biosynthesis and Their Metabolic Engineering in Plants)

  • 하선화;김정봉;박종석;류태훈;김경환;한범수;김종범;김용환
    • Journal of Plant Biotechnology
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    • 제30권1호
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    • pp.81-95
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    • 2003
  • Carotenoids are synthesized from the plastidic glyceraldehyde-3-phosphate (GAP)/pyruvate pathway in isoprenoids biosynthetic system of plants. They play a crucial role in light harvesting, work as photoprotective agents in photosynthesis of nature, and are also responsible for the red, orange and yellow colors of fruits and flowers in plants. In addition to biological actions of carotenoids as antioxidants and natural pigments, they are essential components of human diet as a source of vitamin A. It has been also suggested that some kinds of carotenoids might provide protection against cancer and heart disease as human medicines. In this article, we review the commercial applications on the basis of biological functions of carotenoids, summarize the studies of genes involved in the carotenoid biosynthetic pathway, and introduce recent results achieved in metabolic engineering of carotenoids. This effort for understanding the carotenoids metabolism will make us to increase the total carotenoid contents of crop plants, direct the carotenoid biosynthetic machinery towards other useful carotenoids, and produce a new array of carotenoids by further metabolizing the new precursors that are created when one or two key enzymes in carotenoid biosynthetic pathway are exchanged through gene manipulation in the near future.

KSP inhibitor SB743921 induces death of multiple myeloma cells via inhibition of the NF-κB signaling pathway

  • Song, In-Sung;Jeong, Yu Jeong;Nyamaa, Bayalagmaa;Jeong, Seung Hun;Kim, Hyoung Kyu;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • BMB Reports
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    • 제48권10호
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    • pp.571-576
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    • 2015
  • SB743921 is a potent inhibitor of the spindle protein kinesin and is being investigated in ongoing clinical trials for the treatment of myeloma. However, little is known about the molecular events underlying the induction of cell death in multiple myeloma (MM) by SB743921, alone or in combination treatment. Here, we report that SB743921 induces mitochondria-mediated cell death via inhibition of the $NF-{\kappa}B$ signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the $NF-{\kappa}B$ pathway results in reduced expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. We also found that combination treatment with SB743921 and bortezomib induces death in bortezomib-resistant KMS20 cells. Altogether, these data suggest that treatment with SB743921 alone or in combination with bortezomib offers excellent translational potential and promises to be a novel MM therapy.

새로운 수소 생산 균주인 Enterobacter sp. SNU-1453의 pH에 따른 Metabolic Flux 변화 (pH-dependent Metabolic Flux Shift in Novel Hydrogen-Producing Bacterium Enterobacter sp. SNU-1453)

  • 신종환;윤종현;안은경;심상준;김미선;박태현
    • KSBB Journal
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    • 제20권6호
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    • pp.464-469
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    • 2005
  • 가정쓰레기 매립지 토양에서 분리된 Enterobacter sp. SNU-1453은 Enteric bacteria에 속하는 종(species)으로서 혐기 발효 시 효과적으로 수소를 생산하였다. 이러한 fermentative bacteria는 여러 가지 외부 요인에 의해 다른 metabolism을 나타내어 수소생산량에 영향을 준다. 혐기 발효가 진행됨에 따라 배지의 pH가 급격히 감소하여 미생물 성장과 수소생산에 영향을 미치므로, pH에 따른 metabolism변화를 관찰함으로써 수소생산을 극대화하기 위한 최적 pH 조건을 선정하여 제어할 필요가 있다. 본 연구에서는 수소생산에 대한 pH의 효과 및 pH 제어에 따른 metabolic flux를 분석하였다. 실험 결과 이 분리 균주는 매우 넓은 영역의 pH(4-7.5)에서도 수소를 생산하였으며, pH 7에서 가장 높은 수소생산량을 나타내었다. pH 7로의 제어는 butanediol pathway로부터 수소 생산에 더 유리한 mixed acid fermentation pathway로 metabolic flux를 변화시킴을 알 수 있었다.

Degradation of Polyvinyl Alcohol by Brevibacillus laterosporus: metabolic Pathway of Polyvinyl Alcohol to Acetate

  • Lim, Joong-Gyu;Park, Doo-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제11권6호
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    • pp.928-933
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    • 2001
  • Approximately 0.1 mg/ml of polyvinyl alcohol (PVA) was degraded by the growing cell, Brevibacillus laterospours, for 30 h, and 0.2 mg/ml of PVA was degraded by the cell-free extract that was isolated from Brevibacillus laterosporus. Approximately $0.29{\mu}g$/ml of acetic acid was produced from PVA by using the cell-free extract as a catalyst for 40 min. $V_{max}\;and\;K_m$ value of purified PAV-degradation enzyme was 3.75g/l and 2.75 g/l/min in reaction with EDTA and 3.99 g/l and 2.98 g/l/min in reaction without EDTA, respectively. Molecular weight of the purified enzyme determined by SDS-PAGE was 63,000 Da. Alcohol dehydrogenase and aldehyde dehydrogenase activities were qualitatively detected on a native acrylamide gel by an active staining method, indicating the existence of the metabolic pathway to use PVA as a substrate.

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Simultaneous Utilization of Two Different Pathways in Degradation of 2,4,6-Trinitrotoluene by White Rot Fungus Irpex lacteus

  • 김현영;송홍규
    • 미생물학회지
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    • 제38권4호
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    • pp.250-250
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    • 2002
  • This study confirmed that white rot fungus Irpex lacteus was able to metabolize 2,4,6-trinitrotoluene (TNT) with two different initial transformations. In one metabolic pathway of TNT a nitro group was removed from the aromatic ring of TNT. Hydride-Meisenheimer complexes of TNT (H/sup -/-TNT), colored dark redo were confirmed as the intermediate in this transformation by comparison with the synthetic compounds. 2,4-Dinitrotoluene as a following metabolic product was detected, and nitrite produced by denitration of $H^-$-TNT supported this transformation. In the other TNT pathway, nitro groups in TNT were successively reduced to amino groups via hydroxylamines. Hydroxylamino-dinitrotoluenes and amino-dinitrotoluenes were identified as the intermediates. The activity of a membrane-associated aromatic nitroreductase was detected in the cell-free extract of I. lacteus. This enzyme catalyzed the nitro group reduction of TNT with NADPH as a cofactor, Enzyme activity was not observed in the presence of molecular oxygen.

Estimation of Theoretical Yield for Ethanol Production from D-Xylose by Recombinant Saccharomyces cerevisiae Using Metabolic Pathway Synthesis Algorithm

  • Lee, Tae-Hee;Kim, Min-Young;Ryu, Yeon-Woo;Seo, Jin-Ho
    • Journal of Microbiology and Biotechnology
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    • 제11권3호
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    • pp.384-388
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    • 2001
  • The metabolic pathway synthesis algorithm was applied to estimate the maximum ethanol yield from xylose in a model recombinant Saccharomyces cerevisiae strain containing the genes involved in xylose metabolism. The stoichiometrically independent pathways were identified by constructing a biochemical reaction network for conversion of xylose to ethanol in the recombinant S. cerevisiae. Two independent pathways were obtained in xylose-assimilating recombinant S. cerevisiae as opposed to six independent pathways for conversion of glucose to ethanol. The maximum ethanol yield from xylose was estimated to be 0.46 g/g, which was lower than the known value of 0.51 g/g for glucose-fermenting and wild-type xylose-fermenting yeasts.

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Simultaneous Utilization of Two Different Pathways in Degradation of 2,4,6-Trinitrotoluene by White Rot Fungus Irpex lacteus

  • Kim, Hyoun-Young;Song, Hong-Gyu
    • Journal of Microbiology
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    • 제38권4호
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    • pp.250-254
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    • 2000
  • This study confirmed that white rot fungus Irpex lacteus was able to metabolize 2,4,6-trinitrotoluene (TNT) with two different initial transformations. In one metabolic pathway of TNT a nitro group was removed from the aromatic ring of TNT. Hydride-Meisenheimer complexes of TNT (H$\^$-/-TNT), colored dark redo were confirmed as the intermediate in this transformation by comparison with the synthetic compounds. 2,4-Dinitrotoluene as a following metabolic product was detected, and nitrite produced by denitration of H$\^$-/-TNT supported this transformation. In the other TNT pathway, nitro groups in TNT were successively reduced to amino groups via hydroxylamines. Hydroxylamino-dinitrotoluenes and amino-dinitrotoluenes were identified as the intermediates. The activity of a membrane-associated aromatic nitroreductase was detected in the cell-free extract of I. lacteus. This enzyme catalyzed the nitro group reduction of TNT with NADPH as a cofactor, Enzyme activity was not observed in the presence of molecular oxygen.

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