• 생명과학회지
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• 제32권3호
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• pp.249-255
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• 2022

대사는 생존과 번식에 필수적이다. 2020년에 업그레이드된 COG (cluster of orthologous proteins) 데이터베이스에는 "pathways" 항목이 있다. 본 연구에서는 COG pathways를 이용하여 1,309개의 원핵생물의 대사 경로를 분석하였다. 63개의 대사경로와 관련된 822개의 COG가 있었고, 각 분류단위의 대사관련 COG의 평균은 200.50개(phylum Mollicutes)에서 527.07개(phylum Cyanobacteria)의 사이였다. MPCR을 대사경로구성율(하나의 게놈에 존재하는 COG 수 / 각 대사 경로를 구성하는 COG의 총 수)로 정의하였다. MPCR이 100%인 대사경로의 수는 원핵생물에 따라 0에서 26의 범위였다. 다수의 원핵생물에서 100% MPCR인 대사경로는 세포벽 합성과 관련된 murein biosynthesis (922종), glycine cleavage (918종), ribosome 30S subunits (903종) 등이었다. MPCR이 0%인 대사경로(종의 수)는 photosystem I (1,263종), A/V (archaea/vacuolar)-type ATP synthase (1,028종) 및 Na⁺-translocation NADH dehydrogenase (976종) 등이었다. 원핵생물에 따라 3~49개의 대사경로를 전혀 수행할 수 없었다. MPCR의 보존성이 높은 대사경로의 순서는 ribosome 30S subunit (1,309종의 96.1%), murein biosynthesis (86.8%), arginine biosynthesis (80.4%), serine biosynthesis (80.3%) 및 aminoacyl-tRNA synthetases (82.2%) 등이었다. 단백질과 세포벽 합성이 원핵생물에서 중요한 대사경로인 것을 알 수 있었다. 본 연구의 결과와 원핵생물 사이의 대사경로와 관련된 COG는 항생제 및 인공세포의 개발 등에 활용될 수 있을 것이다.

• IMMUNE NETWORK
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• 제20권6호
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• pp.46.1-46.13
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• 2020

Neutrophils are innate immune cells that constitute the first line of defense against invading pathogens. Due to this characteristic, they are exposed to diverse immunological environments wherein sources for nutrients are often limited. Recent advances in the field of immunometabolism revealed that neutrophils utilize diverse metabolic pathways in response to immunological challenges. In particular, neutrophils adopt specific metabolic pathways for modulating their effector functions in contrast to other immune cells, which undergo metabolic reprogramming to ensure differentiation into distinct cell subtypes. Therefore, neutrophils utilize different metabolic pathways not only to fulfill their energy requirements, but also to support specialized effector functions, such as neutrophil extracellular trap formation, ROS generation, chemotaxis, and degranulation. In this review, we discuss the basic metabolic pathways used by neutrophils and how these metabolic alterations play a critical role in their effector functions.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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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.

• 생명과학회지
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• 제28권3호
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• pp.369-375
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• 2018

Mycoplasma genitalium은 367개의 보존적 유전자를 가지고 있으며 단독배양이 가능한 원핵생물 중 게놈크기가 최소이다. 본 연구에서는 M. genitalium과 M. genitalium보다 보존적 유전자 수가 적은 14개 원핵생물 즉 세포외 공생을 하는 초고온성 고세균 Nanoarchaeum equitans, 식물 세포 내부 기생성 진정세균 혹은 곤충 세포 내부 공생성 진정세균 13종 등의 원핵생물에 보존적인 대사경로를 검토하였다. 이들은 11~71개의 대사경로를 가졌지만 완전한 대사경로는 1~24개였다. 전체 대사경로에 필요한 효소의 45.8%가 결핍되어 대사경로 구멍(metabolic pathway hole)이 매우 많아, 숙주의 효소와 함께 공유대사경로(shared metabolic pathway)를 나타내거나 필수물질의 상당 부분이 숙주에 의존적일 것으로 사료되었다. 세포막을 통한 물질이동에 필요한 유전자의 개수도 아주 적어 단순확산 내지 숙주의 단백질이 이들의 세포막에서 물질이동의 기능을 할 것으로 사료되었다. tRNA charging 경로만이 15개의 분석 대상 원핵생물 모두에 분포하였지만, 분석 대상 원핵생물들은 각각 5~20개의 tRNA charging 유전자를 보유하였다. 본 연구 결과는 배양 불가능한 식물 세포 내 기생성 그리고 곤충 세포 내 공생성 원핵생물들의 대사경로 이해에 대한 단서와 함께 농작물 피해 방지와 해충구제, 의약품 개발 등에 사용할 기초자료를 제공할 수 있을 것이다.

• Journal of Microbiology and Biotechnology
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• 제33권1호
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• pp.114-122
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• 2023

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (β-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.

• Molecules and Cells
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• 제41권4호
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• pp.264-270
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• 2018

Cells cope with diverse intrinsic and extrinsic stimuli in order to make adaptations for survival. The epigenetic landscape plays a crucial role in cellular adaptation, as it integrates the information generated from stimuli. Signaling pathways induced by stimuli communicate with chromatin to change the epigenetic landscape through regulation of epigenetic modifiers. Metabolic dynamics altered by these stimuli also affect the activity of epigenetic modifiers. Here, I review the current understanding of epigenetic regulation via signaling and metabolic pathways. In addition, I will discuss possible ways to achieve specificity of epigenetic modifications through the cooperation of stimuli-induced signal transduction and metabolic reprogramming.

• 한국정보과학회논문지:소프트웨어및응용
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• 제34권5호
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• pp.389-396
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• 2007

서로 다른 종에서의 대사 경로를 비교하는 것은 아직 밝혀지지 않은 유전자를 찾는 문제에 있어 매우 중요하다. 많은 대사 경로 시각화가 제시되었지만 생물학자들은 대사 경로를 단순히 보는 것뿐만 아니라 비교하는 시각화를 필요로 한다. K-Viz는 KEGG 기반의 대사 경로를 위한 시각화 툴이다. 다른 종의 대사 경로를 비교하기 위해 KEGG의 PathComp와 같은 경로를 서로 다른 색으로 표현하는 방법과 각 종에서의 경로를 테이블로 보여준다. K-Viz는 생물학자들이 서로 다른 종에서의 대사 경로 비교를 이해하는데 도움을 준다.

• Genomics & Informatics
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• 제4권3호
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• pp.118-124
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• 2006

For the direct understanding of flow, pathway data are usually represented as directed graphs in biological journals and texts. Databases of metabolic pathways or signal transduction pathways inevitably contain these kinds of graphs to show the flow. KEGG, one of the representative pathway databases, uses the manually drawn figure which can not be easily maintained. Graph layout algorithms are applied for visualizing metabolic pathways in some databases, such as EcoCyc. Although these can express any changes of data in the real time, it exponentially increases the edge crossings according to the increase of nodes. For the understanding of genome scale flow of metabolism, it is very important to reduce the unnecessary edge crossings which exist in the automatic graph layout. We propose a metabolic pathway drawing algorithm for reducing the number of edge crossings by considering the fact that metabolic pathway graph is scale-free network. The experimental results show that the number of edge crossings is reduced about $37{\sim}40%$ by the consideration of scale-free network in contrast with non-considering scale-free network. And also we found that the increase of nodes do not always mean that there is an increase of edge crossings.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.621-629
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• 2021

Shigella flexneri is a facultative intracellular pathogen that causes bacillary dysentery in humans. Infection with S. flexneri can result in more than a million deaths yearly and most of the victims are children in developing countries. Therefore, identifying novel and unique drug targets against this pathogen is instrumental to overcome the problem of drug resistance to the antibiotics given to patients as the current therapy. In this study, a comparative analysis of the metabolic pathways of the host and pathogen was performed to identify this pathogen's essential enzymes for the survival and propose potential drug targets. First, we extracted the metabolic pathways of the host, Homo sapiens, and pathogen, S. flexneri, from the KEGG database. Next, we manually compared the pathways to categorize those that were exclusive to the pathogen. Further, all enzymes for the 26 unique pathways were extracted and submitted to the Geptop tool to identify essential enzymes for further screening in determining the feasibility of the therapeutic targets that were predicted and analyzed using PPI network analysis, subcellular localization, druggability testing, gene ontology and epitope mapping. Using these various criteria, we narrowed it down to prioritize 5 novel drug targets against S. flexneri and one vaccine drug targets against all strains of Shigella. Hence, we suggest the identified enzymes as the best putative drug targets for the effective treatment of S. flexneri.

• 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.