http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Systematic discovery of uncharacterized transcription factors in <i>Escherichia coli</i> K-12 MG1655
Gao, Ye,Yurkovich, James T,Seo, Sang Woo,Kabimoldayev, Ilyas,Drä,ger, Andreas,Chen, Ke,Sastry, Anand V,Fang, Xin,Mih, Nathan,Yang, Laurence,Eichner, Johannes,Cho, Byung-Kwan,Kim, Donghyuk,Palsson, Oxford University Press 2018 Nucleic acids research Vol.46 No.20
<P><B>Abstract</B></P><P>Transcriptional regulation enables cells to respond to environmental changes. Of the estimated 304 candidate transcription factors (TFs) in <I>Escherichia coli</I> K-12 MG1655, 185 have been experimentally identified, but ChIP methods have been used to fully characterize only a few dozen. Identifying these remaining TFs is key to improving our knowledge of the <I>E. coli</I> transcriptional regulatory network (TRN). Here, we developed an integrated workflow for the computational prediction and comprehensive experimental validation of TFs using a suite of genome-wide experiments. We applied this workflow to (i) identify 16 candidate TFs from over a hundred uncharacterized genes; (ii) capture a total of 255 DNA binding peaks for ten candidate TFs resulting in six high-confidence binding motifs; (iii) reconstruct the regulons of these ten TFs by determining gene expression changes upon deletion of each TF and (iv) identify the regulatory roles of three TFs (YiaJ, YdcI, and YeiE) as regulators of <SMALL>L</SMALL>-ascorbate utilization, proton transfer and acetate metabolism, and iron homeostasis under iron-limited conditions, respectively. Together, these results demonstrate how this workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs in parallel.</P>
Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow
Brunk, Elizabeth,Chang, Roger L.,Xia, Jing,Hefzi, Hooman,Yurkovich, James T.,Kim, Donghyuk,Buckmiller, Evan,Wang, Harris H.,Cho, Byung-Kwan,Yang, Chen,Palsson, Bernhard O.,Church, George M.,Lewis, Nat National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.43
<P>Understanding the complex interactions of protein posttranslational modifications (PTMs) represents a major challenge in metabolic engineering, synthetic biology, and the biomedical sciences. Here, we present a workflow that integrates multiplex automated genome editing (MAGE), genome-scale metabolic modeling, and atomistic molecular dynamics to study the effects of PTMs on metabolic enzymes and microbial fitness. This workflow incorporates complementary approaches across scientific disciplines; provides molecular insight into how PTMs influence cellular fitness during nutrient shifts; and demonstrates how mechanistic details of PTMs can be explored at different biological scales. As a proof of concept, we present a global analysis of PTMs on enzymes in the metabolic network of Escherichia coll. Based on our workflow results, we conduct a more detailed, mechanistic analysis of the PTMs in three proteins: enolase, serine hydroxymethyltransferase, and transaldolase. Application of this workflow identified the roles of specific PTMs in observed experimental phenomena and demonstrated how individual PTMs regulate enzymes, pathways, and, ultimately, cell phenotypes.</P>