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- 저자 : Zengler, Karsten (검색결과 4 건)
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Unraveling interactions in microbial communities - from co-cultures to microbiomes
Justin Tan,Cristal Zuniga,Karsten Zengler 한국미생물학회 2015 The journal of microbiology Vol.53 No.5
Microorganisms do not exist in isolation in the environment. Instead, they form complex communities among themselves as well as with their hosts. Different forms of interactions not only shape the composition of these communities but also define how these communities are established and maintained. The kinds of interaction a bacterium can employ are largely encoded in its genome. This allows us to deploy a genomescale modeling approach to understand, and ultimately predict, the complex and intertwined relationships in which microorganisms engage. So far, most studies on microbial communities have been focused on synthetic co-cultures and simple communities. However, recent advances in molecular and computational biology now enable bottom up methods to be deployed for complex microbial communities from the environment to provide insight into the intricate and dynamic interactions in which microorganisms are engaged. These methods will be applicable for a wide range of microbial communities involved in industrial processes, as well as understanding, preserving and reconditioning natural microbial communities present in soil, water, and the human microbiome.
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Deciphering the regulatory codes in bacterial genomes.
Cho, Byung-Kwan,Palsson, Bernhard,Zengler, Karsten Wiley 2011 Biotechnology Journal Vol.6 No.9
<P>Interactions between cis-regulatory elements and trans-acting factors are fundamental for cellular functions such as transcription. With the revolution in microarrays and sequencing technologies, genome-wide binding locations of trans-acting factors are being determined in large numbers. The richness of the genome-scale information has revealed that the nature of the bacterial transcriptome and regulome are considerably more complex than previously expected. In addition, the emerging view of the bacterial transcriptome is revising the concept of the operon organization of the genome. This review describes current advances in the genome-scale analysis of the interaction between cis-regulatory elements and trans-acting factors in microorganisms.</P>
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Deciphering the transcriptional regulatory logic of amino acid metabolism
Cho, Byung-Kwan,Federowicz, Stephen,Park, Young-Seoub,Zengler, Karsten,Palsson, Bernhard ? Nature Publishing Group, a division of Macmillan P 2012 NATURE CHEMICAL BIOLOGY Vol.8 No.1
Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and gene expression data for the transcription factors ArgR, Lrp and TrpR showed that 19 out of 20 amino acid biosynthetic pathways are either directly or indirectly controlled by these regulators. Classifying the regulated genes into three functional categories of transport, biosynthesis and metabolism leads to the elucidation of regulatory motifs that constitute the integrated network's basic building blocks. The regulatory logic of these motifs was determined on the basis of relationships between transcription factor binding and changes in the amount of transcript in response to exogenous amino acids. Remarkably, the resulting logic shows how amino acids are differentiated as signaling and nutrient molecules, revealing the overarching regulatory principles of the amino acid stimulon.
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Determining the Control Circuitry of Redox Metabolism at the Genome-Scale
Federowicz, Stephen,Kim, Donghyuk,Ebrahim, Ali,Lerman, Joshua,Nagarajan, Harish,Cho, Byung-kwan,Zengler, Karsten,Palsson, Bernhard,Burkholder, William F. Public Library of Science 2014 PLoS genetics Vol.10 No.4
<▼1><P>Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism <I>Escherichia coli</I>, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs), ArcA and Fnr of <I>E. coli</I>, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r<SUP>2</SUP> (p<1e-6) correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.</P></▼1><▼2><P><B>Author Summary</B></P><P>All heterotrophic organisms must balance the deployment of consumed carbon compounds between growth and the generation of energy. These two competing objectives have been shown, both computationally and experimentally, to exist as the principal dimensions of the function of metabolic networks. Each of these dimensions can also be thought of as the familiar metabolic functions of catabolism, anabolism, and generation of energy. Here we detail how two global transcription factors (TFs), ArcA and Fnr of <I>Escherichia coli</I> that sense redox ratios, act on a genome-wide basis to coordinately regulate these global metabolic functions through transcriptional control of enzyme and transporter levels in changing environments. A model results from the study that shows how global transcription factors regulate global dimensions of metabolism and form a regulatory hierarchy that reflects the structural hierarchy of the metabolic network.</P></▼2>
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