Team:Bielefeld-CeBiTec/Results/Modelling/erster/test/123

From 2014.igem.org

(Difference between revisions)
(conclusion added)
 
(30 intermediate revisions not shown)
Line 1: Line 1:
-
{{Template:Team:Bielefeld-CeBiTec/igem.css}}
+
<br>
-
{{Template:Team:Bielefeld-CeBiTec/main.css}}
+
-
{{Template:Team:Bielefeld-CeBiTec/Banner_team.css}}
+
-
{{Template:Team:Bielefeld-CeBiTec/Banner_results.tmpl}}
+
-
<html>
+
-
<style>
+
-
flag.flag_element6{
+
-
      background-image:url("https://static.igem.org/mediawiki/2014/0/00/Bielefeld-CeBiTec_14-06-07_Ribbon_middle_rev.png");
+
-
      background-size: 100% 100%;
+
-
      width: auto;
+
-
      height:40px;
+
-
      padding-left: 10px;
+
-
      padding-right: 10px;
+
-
      float:left;
+
-
}
+
-
</style>
+
-
 
+
<a href="https://2014.igem.org/Team:Bielefeld-CeBiTec/Results/Modelling"> Modelling </a>
-
 
+
-
 
+
-
<h1>Modelling</h1>
+
-
 
+
-
 
+
-
<div class="element" style="margin:10px; padding:10px">
+
-
 
+
-
 
+
-
<br><br>
+
-
<h2>Abstract</h2>
+
-
<div id="text">
+
-
  <p>
+
-
We used the following modelling approaches to identify bottlenecks in the constructed pathways and to predict the formation of a desired product in a given time. First of all we created a map of all metabolic reactions which are part of our project (figure 1). This is a usefull tool to give a first overview. Due to the huge amount of components it seems not feasible to create a computational model for all of these reactions at once. Therefore we started our modelling work by carrying out a stochiometric analysis. Afterwards we started a break down of the project in different parts. Dynamic modelling of the metabolites by creating kinetic equations was carried out for the isobutanol production pathway. This was done to identify bottlenecks. Finally we extended the existing model by adding some of the carbon dioxide fixing reactions.
+
-
</p>
+
-
</div>
+
-
<br><br>
+
-
 
+
-
<br><br>
+
-
<h2>Introduction</h2>
+
-
<div id="text">
+
-
  <p>
+
-
Mathematical modelling is essentiell to understand complex biological systems (<a href="#schaber2009">Schaber et al., 2009</a>). The analysis of isolated biological components is supplemented by a systems biology approach since ten years ago (<a href="#chuang2010">Chuang et al., 2010</a>). Mathematical modelling is used to combine biological results (<a href="#kherlopian2008">Kherlopian et al., 2008</a>). Modelling is also a way to gain results without carrying out experiments in a laboratory. The behaviour of a system can be simulated to get results which cannot be derived from simply looking at the given system (<a href="#schaber2009">Schaber et al., 2009</a>).
+
-
The most important aim of any modelling approach is the reduction of complexity. The given biological reality is often very divers and variable. Therefore it is important to identify the major rules and principles which can describe a system.
+
-
</p>
+
-
</div>
+
-
<br><br>
+
-
 
+
-
Our aims were
+
-
<ul>
+
-
<li>visualization of the complete meatoblic network </li>
+
-
<li>relating electron input to product output </li>
+
-
<li>relating electron input to carbon dioxide fixation </li>
+
-
<li>the identification of bottlenecks in the isobutanol production pathway </li>
+
-
<li>prediction of isobutanol production. </li>
+
-
</ul>
+
-
 
+
-
 
+
-
<br><br>
+
-
<br><br>
+
-
<h2>Stoichiometric analysis</h2>
+
-
<div id="text">
+
-
<p>
+
-
We calculated the stoichiometric relations of all substances involved in our complex reaction network (figure 1). The calculation starts with the electrons. They are transported into the system by mediators. We calculated the resulting production of intracellular molecules based on our map of the metabolic system (figure 1). The results are listed below.
+
-
</div>
+
-
</p>
+
-
 
+
-
<br><br>
+
-
 
+
-
 
+
-
<center>
+
-
<div class="element" style="width:750px">
+
-
      <a href="https://static.igem.org/mediawiki/2014/5/53/Bielefeld-CeBiTec_14-10-14_complete_metabolic_system.jpg" target="_blank"><img src="https://static.igem.org/mediawiki/2014/5/53/Bielefeld-CeBiTec_14-10-14_complete_metabolic_system.jpg" width="750px"></a><br>
+
-
      <font size="2" style="text-align:left;">
+
-
<b>Figure 1</b>: Complete metabolic network of reactions which describes our project. </font>
+
-
</div>
+
-
</center>
+
-
 
+
-
<div id="text">
+
-
<p>
+
-
The theoretical electron costs of different molecules is listed in table 1. All calculations are based on our pathway map. The housekeeping metabolism of <i>E. coli</i> is ignored.
+
-
In theory and according to our pathway map there are 42 electrons needed for the production of one molecule isobutanol if CO<sub>2</sub> is used as sole carbon source. Our calculation does not involve the house keeping metabolism of <i>E. coli</i> which consumes lots of energy for the survival of the cell. The number of consumed electrons per produced isobutanol molecule is therefore much higher. The applied electric power can be converted into a number of electrons by the following equation: 1 A = 1 C * s<sup>-1</sup> = 6.2415065 * 10<sup>18</sup> electrons.
+
-
</p>
+
-
</div>
+
-
 
+
-
<br><br>
+
-
<b>Table1:</b> This table shows the theoretical electron costs of different intracellular molecules. The electron costs is the number of electrons which are needed for the synthesis of this metabolite.
+
-
 
+
-
<table width="100%" border="1" cellpadding="5" style="background-color:transparent">
+
-
<tr>
+
-
<th>Substance</th>
+
-
<th>Number of electrons</th>
+
-
</tr>
+
-
<tr> <td>FADH<sub>2<sub></td>  <td>2</td></tr>
+
-
<tr> <td>NADH+H<sup>+</sup></td>  <td>2</td></tr>
+
-
<tr> <td>ATP</td>  <td>1</td></tr>
+
-
<tr> <td>Triosephosphate</td> <td>21</td></tr>
+
-
<tr> <td>CO<sub>2</sub> fixation</td> <td>7</td></tr>
+
-
<tr> <td>Pyruvate</td> <td>19</td></tr>
+
-
<tr> <td>Isobutanol</td> <td>42</td></tr>
+
-
</table>
+
-
 
+
-
 
+
-
<br><br>
+
-
<br><br>
+
-
<h2> Dynamic modelling </h2>
+
-
<div id="text">
+
-
<p>
+
-
After the stoichiometric analysis of the system we decided to use a dynamic model with kinetic equations for the metabolite concentrations. It allows the identification of metabolic or enzymatical bottlenecks. This is our major aim. At least we would like to identify them. Maybe we could even use this information in the next step to modify constructs e.g. exchange a RBS or a promotor sequence. This could be necessary to optimize the different enzyme concentrations. Beside that it was our aim to predict the production of isobutanol per substrate. An improvement of this model could predict the isobutanol production in a carbon dioxide fixing cell.
+
-
To achieve our aims we broke down the complex system shown in figure 1. It was reduced to the system shown in figure 2. This reduced version was suitable for modelling.
+
-
</p>
+
-
</div>
+
-
 
+
-
 
+
-
<br><br>
+
-
<center>
+
-
<div class="element" style="width:750px">
+
-
      <a href="https://static.igem.org/mediawiki/2014/b/ba/Bielefeld-CeBiTec_14-10-14_reduced_metabolic_system.jpg" target="_blank"><img src="https://static.igem.org/mediawiki/2014/b/ba/Bielefeld-CeBiTec_14-10-14_reduced_metabolic_system.jpg" width="750px"></a><br>
+
-
      <font size="2" style="text-align:left;">
+
-
<b>Figure 2</b>: Reduced metabolic network of reactions which were selected for modelling. </font>
+
-
</div>
+
-
</center>
+
-
<br><br>
+
-
 
+
-
<h3>Isobutanol production pathway</h3>
+
-
<div id="text">
+
-
<p>
+
-
We started our modelling work on the <a href="https://2014.igem.org/Team:Bielefeld-CeBiTec/Project/Isobutanol/GeneticalApproach">isobutanol pathway</a> by reading publications about the isobutanol production pathway <a href="#atsumi2008">(Atsumi et al., 2008</a> and <a href="#atsumi2010"> Atsumi et al., 2010)</a>. Doing that we collected a lot of information. The first modelling approach was a system of differential equations using Michealis-Menten kinetics. This was published as the best approach if reaction kinetics are not known (<a href="#breitling2008">Breitling et al., 2008</a>; <a href="#chubukov2014">Chubukov et al., 2014</a>). All needed k<sub>cat</sub> and K<sub>M</sub> values were collected from the literature and from databases like <a href=“http://www.genome.jp/kegg/“>KEGG</a>, <a href=“http://biocyc.org/“>biocyc</a> and <a href=“http://www.brenda-enzymes.org/“>BRENDA </a>(table 2). Missing values were replaced by estimations.
+
-
The starting concentrations for different metabolites were also taken from the literature and from different databases (table 3).
+
-
</p>
+
-
</div>
+
-
 
+
-
 
+
-
<br><br>
+
-
<b>Table2:</b> This table shows all enzymatic parameters which were used for our first model.
+
-
 
+
-
 
+
-
<table width="100%" border="1" cellpadding="5" style="background-color:transparent">
+
-
<tr>
+
-
<th>Enzyme</th>
+
-
<th>k<sub>cat</sub></th>
+
-
<th>K<sub>M</sub> [mM]</th>
+
-
<th>Reference</th>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>AlsS</td> <td>121</td> <td>13.6</td> <td><a href="#atsumi2009">Atsumi et al., 2009</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>IlvC</td> <td>2.2</td> <td>0.25</td> <td><a href="#tyagi2005">Tyagi et al., 2005</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>IlvD</td> <td>10 (estimated)</td> <td>1.5</td> <td><a href="#flint1993">Flint et al., 1993</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>KivD</td> <td>20 (estimated)</td> <td>5 (estimated)</td> <td><a href="#werther2008">Werther et al., 2008</a>; <a href="#gorcke2007">Gorcke et al., 2007</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>AdhA</td> <td>6.6</td> <td>9.1</td> <td><a href="#atsumi2010">Atsumi et al., 2010</a></td>
+
-
</tr>
+
-
 
+
-
</table>
+
-
<br><br>
+
-
 
+
-
 
+
-
 
+
-
<br><br>
+
-
<b>Table3:</b> This table shows all metabolite concentrations which were used for our first model. The metabolite concentration was set to zero, if no published value was available.
+
-
 
+
-
<table width="100%" border="1" cellpadding="5" style="background-color:transparent">
+
-
<tr>
+
-
<th>Metabolite</th>
+
-
<th>Concentration [mM]</th>
+
-
<th>Reference</th>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>Pyruvate</td> <td>10</td> <td><a href="#yang2000">Yang et al., 2000</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>2-Acetolactate</td> <td>-</td> <td>-</td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>2,3-Dihydroxyisovalerate</td> <td>-</td> <td>-</td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>2-Ketoisovalerate</td> <td>-</td> <td>-</td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>Isobutyraldehyde</td> <td>0.6</td> <td></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>Isobutanol</td> <td>variable</td> <td>-</td>
+
-
</tr>
+
-
</table>
+
-
<br><br>
+
-
<div id="text">
+
-
<p>
+
-
 
+
-
 
+
-
We implemented the system of differential equations (figure 3) in matlab (link to source code) and created first results. The predicted changing of the metabolic concentration over the time is shown in figure 4.
+
-
</p>
+
-
</div>
+
-
 
+
-
 
+
-
<br><br>
+
-
<center>
+
-
<div class="element" style="width:750px">
+
-
      <a href="https://static.igem.org/mediawiki/2014/7/7e/Bielefeld-CeBiTec_14_10_16_dgls.png" target="_blank"><img src="https://static.igem.org/mediawiki/2014/7/7e/Bielefeld-CeBiTec_14_10_16_dgls.png" width="750px"></a><br>
+
-
      <font size="2" style="text-align:left;">
+
-
<b>Figure 4</b>: Differential equations for the dynamic modelling of the isobutanol production. </font>
+
-
</div>
+
-
</center>
+
-
<br><br>
+
-
 
+
-
 
+
-
 
+
-
<center>
+
-
<div class="element" style="width:750px">
+
-
      <a href="https://static.igem.org/mediawiki/2014/6/6b/Bielefeld-CeBiTec_14-10-14_modelling_1.png" target="_blank"><img src="https://static.igem.org/mediawiki/2014/6/6b/Bielefeld-CeBiTec_14-10-14_modelling_1.png" width="750px"></a><br>
+
-
      <font size="2" style="text-align:left;">
+
-
<b>Figure 4</b>: Predicted changes in metabolic concentration over time. </font>
+
-
</div>
+
-
</center>
+
-
 
+
-
 
+
-
<br><br>
+
-
 
+
-
<div id="text">
+
-
<p>
+
-
The amount of expressed proteins could differ depending on the distance of the coding sequence downstream of the promotor. Different values can be used to simulate the usage of promotors of different strength. This approach also allows the modelling of different growth states. The growth is represented by an increase in the amount of enzyme.
+
-
 
+
-
Our modelling results indicated that the concentration of <a href="https://2014.igem.org/Team:Bielefeld-CeBiTec/Project/Isobutanol/GeneticalApproach">IlvC</a> is limiting the isobutanol production. An experimentell verification of this hind is the next logical step. This bottleneck could be removed by overexpression of the corresponding coding sequence. One way to achieve this is the integration of a strong promotor and RBS upstream of this coding sequence. Due to a lack of time we were not able to follow up this lead. It could be a great possibility to improve our isobutanol production.
+
-
</p>
+
-
 
+
-
 
+
-
 
+
-
<br><br>
+
-
 
+
-
<h3>Carbon dioxide fixing reactions</h3>
+
-
 
+
-
 
+
-
<p>
+
-
The next model improvement was the addition of some of the carbon fixing reactions and the pathway leading to pyruvate. We collected k<sub>cat</sub> and K<sub>M</sub> values for nearly all relevant steps (table 4). They were used for differential equations which describe these additional reactions.
+
-
</p>
+
-
</div>
+
-
 
+
-
 
+
-
<br><br>
+
-
<b>Table4:</b> This table shows all k<sub>cat</sub> and K_<sub>M</sub> values of enzymes involved in CO<sub>2</sub>-fixation and the pathway leading to pyruvate.
+
-
<table width="100%" border="1" cellpadding="5" style="background-color:transparent">
+
-
<tr>
+
-
<th>Enzyme</th>
+
-
<th>k<sub>cat</sub></th>
+
-
<th>K<sub>M</sub> [mM]</th>
+
-
<th>Reference</th>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>PrkA</td>         <td>72.6</td> <td>0.09</td> <td><a href="#wadano1998">Wadano et al., 1998</a>,<a href="#kobayashi2003">Kobayashi et al., 2003</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>RubisCO</td> <td>20 (estimated)</td> <td>0.02 (estimated)</td> <td><a href="#lan1991">Lan and Mott, 1991</a>,<a href="#sage2002">Sage, 2002</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>Pgk</td> <td>480</td> <td>1 (estimated)</td> <td><a href="#fifis1978">Fifis and Scopes., 1978</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>GapA</td> <td>-</td> <td>0.5</td> <td><a href="#zhao1995">Zhao et al., 1995</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>GpmA</td> <td>490 (in <i>S.cerevisiae</i>)</td> <td>0.15</td> <td><a href="#fraser1999">Fraser et al., 1999</a>,<a href="#white1992">White and Fothergil-Gilmore, 1992</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>Eno</td> <td>17600</td> <td>0.1</td> <td><a href="#spring1972">Spring and Wold, 1972</a>, <a href="#albe1990">Albe et al., 1990</a></td>
+
-
</tr>
+
-
 
+
-
<tr>
+
-
<td>PykF</td> <td>3.2</td> <td>0.3 (estimated)</td> <td><a href="#oria2005">Oria-Hernandez et al., 2005</a></td>
+
-
</tr>
+
-
</table>
+
-
<br><br>
+
-
 
+
-
 
+
-
 
+
-
<br><br>
+
-
 
+
-
<h2>Conclusion and summary</h2>
+
-
We were able to achieve most our aims. The complete metabolic network of our project is visualized in figure 1. Stoichiometric caculations revealed the number of electrons which is in theory need for the production of a desired substance. There are 42 electrons needed for the synthesis of one molecule isobutanol. The fixation of one carbon dioxide molecule would cost 7 electrons. We were able to identify a putative bottleneck in the isobutanol production pathway. This needs to be verified by experiments. The production of isobutanol from pyruvate can be predicted.
+
-
The next and very important step would be the verification of these prediction by experimental approaches.
+
-
 
+
-
 
+
-
 
+
-
 
+
-
 
+
-
 
+
-
<br><br>
+
-
 
+
-
<div class="element">
+
-
  <div id="text">
+
-
  <h6>References</h6>
+
-
<ul>
+
-
+
-
<li id="atsumi2008">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Atsumi, Shota, Taizo Hanai, und James C. Liao. „Non-Fermentative Pathways for Synthesis of Branched-Chain Higher Alcohols as Biofuels“. <a href="http://www.nature.com/nature/journal/v451/n7174/full/nature06450.html">Nature</a> 451, Nr. 7174 (3. Januar 2008): 86–89. doi:10.1038/nature06450.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
<li id="atsumi2010">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Atsumi, Shota, Tung-Yun Wu, Eva-Maria Eckl, Sarah D. Hawkins, Thomas Buelter, und James C. Liao. „Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes“. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802489/">Applied Microbiology and Biotechnology</a> 85, Nr. 3 (Januar 2010): 651–57. doi:10.1007/s00253-009-2085-6.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="yang2000">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Yang, Y. T., G. N. Bennett, und K. Y. San. „The Effects of Feed and Intracellular Pyruvate Levels on the Redistribution of Metabolic Fluxes in Escherichia Coli“. <a href="http://bioc.rice.edu/bennetlab/references/ref40-sdarticle.pdf">Metabolic Engineering</a> 3, Nr. 2 (April 2001): 115–23. doi:10.1006/mben.2000.0166.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="wadamo1998">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Wadano, Akira, Keisuke Nishikawa, Tomohiro Hirahashi, Ryohei Satoh, und Toshio Iwaki. „Reaction Mechanism of Phosphoribulokinase from a Cyanobacterium, Synechococcus PCC7942“. <a href="http://link.springer.com/article/10.1023%2FA%3A1005979801741">Photosynthesis Research</a> 56, Nr. 1 (1. April 1998): 27–33. doi:10.1023/A:1005979801741.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="kobayashi2003">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Kobayashi, Daisuke, Masahiro Tamoi, Toshio Iwaki, Shigeru Shigeoka, und Akira Wadano. „Molecular Characterization and Redox Regulation of Phosphoribulokinase from the Cyanobacterium Synechococcus Sp. PCC 7942“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12668773/">Plant & Cell Physiology</a> 44, Nr. 3 (März 2003): 269–76.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="lan1991">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Lan, Yun, und Keith A. Mott. „Determination of Apparent Km Values for Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase (Rubisco) Activase Using the Spectrophotometric Assay of Rubisco Activity“. <a href="http://www.plantphysiol.org/content/95/2/604.abstract">Plant Physiology</a> 95, Nr. 2 (2. Januar 1991): 604–9. doi:10.1104/pp.95.2.604.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
 
+
-
<li id="sage2002">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Sage, Rowan F. „Variation in the K(cat) of Rubisco in C(3) and C(4) Plants and Some Implications for Photosynthetic Performance at High and Low Temperature“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11886880">Journal of Experimental Botany</a> 53, Nr. 369 (April 2002): 609–20.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
 
+
-
<li id="fifis1978">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Fifis, T., und R. K. Scopes. „Purification of 3-Phosphoglycerate Kinase from Diverse Sources by Affinity Elution Chromatography“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=fifis+1978">The Biochemical Journal</a> 175, Nr. 1 (1. Oktober 1978): 311–19.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
 
+
-
<li id="zhao1995">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Zhao G, Halbur T, Pankratz DC. Colonization of oropharynx and nasal cavity of CDCD pigs by a nontoxigenic strain of Pasteurella multocida type D. <a href="https://www.aasv.org/shap/abstracts/abstract.php?v3n3p113">J Swine Health Prod</a> 1995;3(3):113-115.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="fraser1999">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Fraser, H. I., M. Kvaratskhelia, und M. F. White. „The Two Analogous Phosphoglycerate Mutases of Escherichia Coli“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10437801">FEBS Letters</a> 455, Nr. 3 (23. Juli 1999): 344–48.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="white1992">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
White, Malcolm F., und Linda A. Fothergill-Gilmore. „Development of a Mutagenesis, Expression and Purification System for Yeast Phosphoglycerate Mutase“. <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1992.tb17099.x/pdf">European Journal of Biochemistry</a> 207, Nr. 2 (1. Juli 1992): 709–14. doi:10.1111/j.1432-1033.1992.tb17099.x.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="spring1972">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Spring, Thomas G., und Finn Wold. „The Purification and Characterization of Escherichia Coli Enolase“. <a href="http://www.jbc.org/content/246/22/6797.long">Journal of Biological Chemistry</a> 246, Nr. 22 (25. November 1971): 6797–6802.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="albe1990">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Albe, Kathy R., Margaret H. Butler, und Barbara E. Wright. „Cellular concentrations of enzymes and their substrates“. <a href="http://www.sciencedirect.com/science/article/pii/S0022519305802668">Journal of Theoretical Biology</a> 143, Nr. 2 (22. März 1990): 163–95. doi:10.1016/S0022-5193(05)80266-8.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="oria2005">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Oria-Hernández, Jesús, Nallely Cabrera, Ruy Pérez-Montfort, und Leticia Ramírez-Silva. „Pyruvate Kinase Revisited: The Activating Effect of K+“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16147999">The Journal of Biological Chemistry</a> 280, Nr. 45 (11. November 2005): 37924–29. doi:10.1074/jbc.M508490200.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="breitling2008">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Breitling, Rainer, David Gilbert, Monika Heiner, und Richard Orton. „A Structured Approach for the Engineering of Biochemical Network Models, Illustrated for Signalling Pathways“. <a href="http://bib.oxfordjournals.org/content/9/5/404.short">Briefings in Bioinformatics</a> 9, Nr. 5 (9. Januar 2008): 404–21. doi:10.1093/bib/bbn026.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="chubukov2014">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Chubukov, Victor, Luca Gerosa, Karl Kochanowski, und Uwe Sauer. „Coordination of Microbial Metabolism“. <a href="http://www.nature.com/nrmicro/journal/v12/n5/abs/nrmicro3238.html">Nature Reviews Microbiology</a> 12, Nr. 5 (Mai 2014): 327–40. doi:10.1038/nrmicro3238.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="schaber2009">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Schaber, J., W. Liebermeister, und E. Klipp. „Nested Uncertainties in Biochemical Models“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/19154080">IET Systems Biology</a> 3, Nr. 1 (Januar 2009): 1–9. doi:10.1049/iet-syb:20070042.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
 
+
-
 
+
-
<li id="chuang2010">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Chuang, Han-Yu, Matan Hofree, und Trey Ideker. „A Decade of Systems Biology“. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20604711">Annual Review of Cell and Developmental Biology</a> 26 (2010): 721–44. doi:10.1146/annurev-cellbio-100109-104122.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="kherlopian2008">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Kherlopian, Armen R., Ting Song, Qi Duan, Mathew A. Neimark, Ming J. Po, John K. Gohagan, und Andrew F. Laine. „A Review of Imaging Techniques for Systems Biology“. <a href="http://www.biomedcentral.com/1752-0509/2/74">BMC Systems Biology</a> 2, Nr. 1 (12. August 2008): 74. doi:10.1186/1752-0509-2-74.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="tyagi2005">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Tyagi, R., Lee, Y.-T., Guddat, L.W., and Duggleby, R.G. (2005). Probing the mechanism of the bifunctional enzyme ketol-acid reductoisomerase by site-directed mutagenesis of the active site. <a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2004.04506.x/pdf">FEBS J.</a> 272, 593–602.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="atsumi2009">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Atsumi, S., Li, Z., and Liao, J.C. (2009). Acetolactate Synthase from Bacillus subtilis Serves as a 2-Ketoisovalerate Decarboxylase for Isobutanol Biosynthesis in Escherichia coli. <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753059/">Appl Environ Microbiol</a> 75, 6306–6311.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
<li id="flint1993">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Flint, D.H., Emptage, M.H., Finnegan, M.G., Fu, W., and Johnson, M.K. (1993). The role and properties of the iron-sulfur cluster in Escherichia coli dihydroxy-acid dehydratase. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8325851">J. Biol. Chem.</a> 268, 14732–14742.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="gorcke2007">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Gocke, D., Nguyen, C.L., Pohl, M., Stillger, T., Walter, L., and Müller, M. (2007). Branched-Chain Keto Acid Decarboxylase from Lactococcus lactis (KdcA), a Valuable Thiamine Diphosphate-Dependent Enzyme for Asymmetric CC Bond Formation. <a href="http://onlinelibrary.wiley.com/doi/10.1002/adsc.200700057/pdf">Adv. Synth. Catal.</a> 349, 1425–1435.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
<li id="werther2008">
+
-
<div class="element" style="margin_10px 10px 10px 10px; padding:10px 10px 10px 10px">
+
-
<div id="text">
+
-
Werther, T., Spinka, M., Tittmann, K., Schütz, A., Golbik, R., Mrestani-Klaus, C., Hübner, G., and König, S. (2008). Amino Acids Allosterically Regulate the Thiamine Diphosphate-dependent α-Keto Acid Decarboxylase from Mycobacterium tuberculosis. <a href="http://www.jbc.org/content/283/9/5344.long">J. Biol. Chem.</a> 283, 5344–5354.
+
-
</div>
+
-
</div>
+
-
</li>
+
-
 
+
-
 
+
-
 
+
-
 
+
-
 
+
-
 
+
-
</ul>
+
-
</div>
+
-
</div>
+
-
</div>
+
-
</html>
+

Latest revision as of 19:10, 16 October 2014


<a href="https://2014.igem.org/Team:Bielefeld-CeBiTec/Results/Modelling"> Modelling </a>

Retrieved from "http://2014.igem.org/Team:Bielefeld-CeBiTec/Results/Modelling/erster/test/123"