Difference between revisions of "Team:UPF CRG Barcelona/Simulation"

 
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         <p class="page-title">SIMULATION OF INTESTINE CONDITIONS</p>
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         <p class="page-title">SIMULATION OF INTESTINAL CONDITIONS</p>
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      <p>In the set of our project, it is highly important to know in which environment the genetically modified bacteria is going to be working. In the intestine there is a steep gradient for oxygen; its concentrations decrease precipitously to near anoxia at the midpoint of the lumen [1]. For this reason, if we want our engineered bacteria to properly work in the gut, it has to work under anaerobic conditions as well. However, long chain fatty acids (LCFA) are degraded via the beta-oxidation pathway, an aerobic pathway for excellence, therefore it is necessary to find alternative strategies in order to metabolize LCFA in absence of oxygen.</p>
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<p>Moreover, when engineering a pathway in order to optimize it, it is very important to keep in mind that the overall efficiency of the synthetic pathway can decrease either by the loss of metabolic intermediates by diffusion or by competing pathways [2]. In the intestine, after diet ingestion, there is going to be other energetic substrates aside of LCFA, especially sugars and amino acids. Therefore, most of the catabolic pathways of bacteria are going to be active and can interfere with beta oxidation efficiency. For this reason, it is very important to study the metabolic network as a whole instead of only focusing on the pathway that we want to modify. In order to do so, we performed flux balance analysis simulations to be able to predict PA uptake and bacteria growth taking into account all the aforementioned variables.</p>
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<a href="https://2018.igem.org/Team:UPF_CRG_Barcelona/Model"><button class="button">See model results</button></a>
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<p class="subapart2">References</p>
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<p class="references">[1] Espey, M. (2013). Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota. Free Radical Biology and Medicine, 55, pp.130-140.</p>
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<p class="references">[2] Na, D., Kim, T. and Lee, S. (2010). Construction and optimization of synthetic pathways in metabolic engineering. Current Opinion in Microbiology, 13(3), pp.363-370.</p>
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        <p>It is very important to have in mind in which environment the genetically modified bacteria are going to be
 
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            working. In the intestine, there is a steep gradient for oxygen and its concentrations decrease precipitously
 
−
          near anoxia in the middle of the lumen (Espey, 2013). For this reason, if we want our engineered
 
−
            bacteria to work in the gut, it has to work under anaerobic conditions. However, LCFA are degraded via the
 
−
            beta-oxidation pathway, an aerobic pathway for excellence, therefore it is needed to find alternative
 
−
            strategies in order to metabolize LCFA without oxygen. </p>
 
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          <p>Moreover, when engineering a pathway in order to optimize it, it is very important to have in mind that the
 
−
            overall efficiency of the synthetic pathway can be reduced by the loss of metabolic intermediates by
 
−
            diffusion or by competent pathways (Na, Kim and Lee, 2010]. In the intestine, after diet ingest, there is
 
−
            going to be other energetic substrates aside of LCFA, especially sugars and amino acids. Therefore, most of
 
−
            the catabolic pathways of bacteria are going to be active and can interfere with beta oxidation efficiency.
 
−
            For this reason, it is very important to study the metabolic network as a whole instead of only focusing on
 
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            the pathway that we want to modify. </p>
 
 
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Latest revision as of 02:30, 18 October 2018

Wiki

SIMULATION OF INTESTINAL CONDITIONS

In the set of our project, it is highly important to know in which environment the genetically modified bacteria is going to be working. In the intestine there is a steep gradient for oxygen; its concentrations decrease precipitously to near anoxia at the midpoint of the lumen [1]. For this reason, if we want our engineered bacteria to properly work in the gut, it has to work under anaerobic conditions as well. However, long chain fatty acids (LCFA) are degraded via the beta-oxidation pathway, an aerobic pathway for excellence, therefore it is necessary to find alternative strategies in order to metabolize LCFA in absence of oxygen.

Moreover, when engineering a pathway in order to optimize it, it is very important to keep in mind that the overall efficiency of the synthetic pathway can decrease either by the loss of metabolic intermediates by diffusion or by competing pathways [2]. In the intestine, after diet ingestion, there is going to be other energetic substrates aside of LCFA, especially sugars and amino acids. Therefore, most of the catabolic pathways of bacteria are going to be active and can interfere with beta oxidation efficiency. For this reason, it is very important to study the metabolic network as a whole instead of only focusing on the pathway that we want to modify. In order to do so, we performed flux balance analysis simulations to be able to predict PA uptake and bacteria growth taking into account all the aforementioned variables.

References

[1] Espey, M. (2013). Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota. Free Radical Biology and Medicine, 55, pp.130-140.

[2] Na, D., Kim, T. and Lee, S. (2010). Construction and optimization of synthetic pathways in metabolic engineering. Current Opinion in Microbiology, 13(3), pp.363-370.