Difference between revisions of "Team:Pasteur Paris/Description"

 
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        <img src="https://static.igem.org/mediawiki/2015/4/42/Plasticure.jpg" style="width: 100%;"/>
  <h1><font size=10><center>PlastiCure</center></font></h1>
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<br/><br/><br/>
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<p class="titrepage">The Problem</p>
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    <div align="justify"><p style="text-indent:3em;">Every year, more and more plastics are produced. In 2000, the world plastic production was about <b>190 million tons per year</b> whereas today, it is roughly <b>300 million tons per year</b> (Fig.1). The most common plastics are polyethylene (PE), polyethylene terephthalate (PET) and polypropylene (PP).
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      <p><center><img src="https://static.igem.org/mediawiki/2015/d/d2/IGEM_Pasteur_world_plastics_production.jpg" style="height:50%; width:50%" /> </center></p>
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      <center><p><b>Fig.1</b> - Evolution of the world plastic production, in million of tons, from 1950 to 2020.<sup><b>1</b></sup></p></center>
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      </br></div>
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<div align="justify"><p style="text-indent:3em;"> However, the treatment of plastic is not yet <b>suited</b> to the exponential growth of plastic production. <b>In 2012</b>, Europe produced <b>25.2 million tons of plastic waste</b><sup>2</sup>, among which only <b>26%</b> were recycled. The remaining 74% were either burned in order to produce energy (<b>36%</b>) or dumped and buried (<b>38%</b>). This leads to an increase in plastic in nature which pollutes our ecosystem, especially the <b>oceans</b>.</p>
  
  <h4 style="font-size:25px"><u>The Problem:</u></h4>
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    <p><center><img src="https://static.igem.org/mediawiki/2015/4/43/IGEM_Pasteur_plastics_waste_from_Europe.jpg" style="height:35%; width:35%" /> </center></p>
    <div align="justify"><p style="text-indent:3em;">Every year, more and more plastics are produced. <b>In 2000, 190 million tons </b>of plastic were produced in the world, whereas <b>today, approximatively 300 million tons</b> of plastic are produced (Fig.1). The most produced types of plastic are polyethylene (PE), polyethylene terephthalate (PET) and polypropylene (PP).</p>
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<center><p><b>Fig.2</b> - Treatment of post-consumer plastics waste in 2012, in the European Union.<sup><b>3</b></sup></p></center>
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</br></div>
 
      
 
      
    <p><center><img src="https://static.igem.org/mediawiki/2015/d/d2/IGEM_Pasteur_world_plastics_production.jpg" style="height:50%; width:50%" /> </center></p>
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<div align="justify"><p style="text-indent:3em;">The problem is worsened by the size of the plastic particles: they are mostly <b>microparticles</b>. Indeed, over 90% of the ocean’s plastic particles measure <b>less than 5mm</b>. This makes it difficult to clean the plastic out of the ocean.
<center><p><b>Fig.1</b> - Evolution of the world plastic production, in million of tons, since 1950 to 2020.<sup><b>1</b></sup></p></center>
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The greatest danger comes from invisible plastic since the particles are becoming small enough to be accidentally ingested by <b>zooplankton</b>.<b><sup>4</sup></b>
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Indeed, oxidation and UV radiation can break the plastic into small fragments which can attain a minimum size of <b>20µm</b>. The plastic then works its way up our <b>food chain</b> and ends up on our plates.<b><sup>5</sup></b>
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</p>
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<div id="link_solution"></div>  
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</br></br></br></div>
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        <br/><br/>
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<p class="titrepage">Our solution</p>
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<div class="carregris">
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      <div align="justify"><p style="text-indent:3em;"><b>PlastiCure</b> is a biological system designed to degrade <b>PET</b> and use the degradation products to synthesize <b>bio-active compounds</b>. The idea is to create a new way to <b>treat plastic waste</b> by degrading it into a novel profitable transformation product and then increase efforts in plastic recycling.
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</p>
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</br>
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      <p style="text-indent:3em;">The challenge of the project is to <b>combine</b> in one system a PET degradation pathway with an optimized biosynthetic pathway: we aim to transform plastic waste into a profitable life-saving drug, erythromycin A. This constitutes a revalorisation of plastic waste into drug.
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<i>E. coli</i> will be used as a <b>heterologous host</b> to integrate <b>exogenous DNA sequences</b> in <b>multiple operons</b> (82 % of our designed operons will be composed of heterologous genes).
 +
This will allow <i>E. coli</i> to express all of the necessary biodegradation and biosynthesis genes.</p>
 
</br>
 
</br>
<div align="justify"><p style="text-indent:3em;">However, today, the treatment of plastic waste is not adapted to this exponential production… <b>In 2012, 25.2 million tons of plastic waste</b> were produced in Europe<sup><b>2</b></sup>, among which only <b>26 %</b> were recycled, while <b>36 %</b> were burned in order to produce energy and the remaining <b>38 %</b> were dumped or buried (Fig.2). In the end, this plastic accumulate in nature and pollute our ecosystem, especially the <b>oceans</b>.
 
  
    <p><center><img src="https://static.igem.org/mediawiki/2015/4/43/IGEM_Pasteur_plastics_waste_from_Europe.jpg" style="height:40%; width:40%" /> </center></p>
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      <p> <center><img src="https://static.igem.org/mediawiki/2015/3/30/Igem-Pasteur_Bacterie-PlastiCure.png" style="height:60%; width:60%" /> </center></p>
<center><p><b>Fig.2</b> - Treatment for post-consumer plastics waste in 2012, in the European Union.<sup><b>3</b></sup></p></center>
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  <center><p><b>Fig.3</b> - Our <i>E. coli</i> system is able to synthesize biologically active products and at the same time degrade plastic waste.</p></center>
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</br>
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<p style="text-indent:3em;"> Erythromycin is an <b>antibiotic</b> used to treat bacterial infections in cases of allergy to penicillin.  It is hence a <b>frequently prescribed</b> drug. Erythromycin also has an important role in the <b>hemi synthesis</b> of new active ingredients. Despite a very <b>important demand</b>, the total synthesis of erythromycin A remains a very long and complex process of about 50 stages. It is therefore an <b>expensive process</b>.<b><sup>6</sup></b></p>
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<br/>
  
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      <p style="text-indent:3em;">Recent advances in synthetic biology enabled erythromycin production in <i>E. coli</i>. B. Pfeifer and H. Zhang designed a system of <b>4 plasmids</b> working in the <i>E. coli</i> BAP 1 strain and leading to erythromycin A production with a <b>yield of 10 mg per liter of culture media</b>.<sup><b>7</b></sup> </p>
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  <p><center><img src="https://static.igem.org/mediawiki/2015/d/d3/1280px-Erythromycin_A.svg.jpeg" style="height:45%; width:45%" /></center></p>
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  <center><p><b>Fig.4</b> - The very complex molecule of erythromycin A.<sup><b>8</b></sup></center></p>
 
</br>
 
</br>
    <div align="justify"><p style="text-indent:3em;">The problem is accentuated by the fact that plastic waste are <b>microparticles</b>: in our oceans, more than 90% of the plastic particles are <b>smaller than 5 mm</b>, which makes it almost impossible to clean the oceans.
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The worst danger comes from invisible plastic: the oxidation, but especially the ultraviolet radiation, cause fragmentation of plastics smaller and smaller, which can reach <b>20 micrometers</b> in diameter. Today, the particles are becoming small enough to enter in our <b>food chain</b>.<sup><b>4</b></sup>
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      <p style="text-indent:3em;"> <b>PlastiCure</b> is a well-designed biological system composed of <b>2 parts</b>: degradation and synthesis. The PET degradation part is composed of 2 pathways: terephthalic acid (green arrows) and ethylene glycol (blue arrows). In total, the two pathways are composed of 15 genes <b>(~22 kb)</b>, that will be integrated in an operon into one plasmid.</p></div>
 
</br>
 
</br>
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      <p> <center><img src="https://static.igem.org/mediawiki/2015/6/63/Chaine_de_degradation_-_copie.png" style="height:42%; width:42%" /> </center>
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  <center><b>Fig.5</b> - Degradation pathway of the system.</p></center>
 
</br>
 
</br>
    <h4 style="font-size:25px"><u>Our solution:</u></h4>
 
  
       <div align="justify"><p style="text-indent:3em;"><b>PlastiCure</b> is a biological system based on <i><b>E. coli</i></b> designed to degrade plastics and use the degradation products to produce <b>bio-active compounds</b>. The challenge of the project is to <b>coupling these two biosynthetic pathways in one system</b>. The idea here is first to create a new way to <b>treat plastic waste</b> but also to produce from plastic a novel profitable transformation product that will increase efforts in plastic recycling.</p>
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       <p style="text-indent:3em;"> Erythromycin A is synthesized by a modular <b>Polyketide Synthase (type 1)</b>. The products of degradation, <b>propionyl-CoA</b> and <b>(S)-Methylmalonyl-CoA</b>, are used to synthesize <b>6-deoxyerythronolide B (6deB)</b>. <b>Ery operon enzymes</b> will make erythromycin A using 6deB as a precursor.</p>
 
</br>
 
</br>
       <p style="text-indent:3em;">By engineering the metabolism of <i>E. coli</i> we want to create a system able to produce a <b>curative product, the erythromycin</b>, and in the same time help to address the issue of <b>plastic pollution</b>. Therefore, <i>E. coli</i> will be used as a <b>heterologous host</b> to integrate <b>exogenous DNA sequences</b>, well-organsied in <b>multiple operons</b> (82 % of our designed operons will be composed of heterologous genes). By this NEW WAY we will allowed <i>E. coli</i> to express all biodegration / biosynthesis genes and so we will favorise the <b>revalorisation</b> of the plastic waste into drug.</p>
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       <p> <center><img src="https://static.igem.org/mediawiki/2015/4/40/BAP1.png" style="height:45%; width:45%" /> </center></p>
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  <center><p><b>Fig.6</b> - Propionate metabolism in <i>E. coli</i> BAP 1.</p></center>
 
</br>
 
</br>
  <p> <center><img src="https://static.igem.org/mediawiki/2015/e/ea/Schéma_iGEM_Pasteur.jpg" style="height:70%; width:70%" /> </center></p>
 
</br>
 
      <p style="text-indent:3em;">Erythromycin is an <b>antibiotic</b> used by people who are found to be allergic to penicillin to treat bacteria infections by preventing them from growing and multiplying. This drug is <b>popular</b> and common man is aware of them because of it being <b>prescribed frequently</b> by doctors. <b>Demand is consequently very important</b>. But today the total synthesis of erythromycin is very complex : about <b>50 stages</b>, which are increasing the synthesis <b>duration and cost</b>.<sup><b>5</b></sup></p>
 
</br>
 
  <p> <center><img src="https://en.wikipedia.org/wiki/Erythromycin#/media/File:Erythromycin_A.svg" style="height:70%; width:70%" /> </center></p>
 
  <center><p><b>Fig.4</b> - The very complex molecule of erythromycin A.<sup><b>6</b></sup></center></p>
 
</br>
 
      <p style="text-indent:3em;">Moreover, PlastiCure is a biological system well-designed, In fact, we can think of removing the erythromycin pathway to insert other pathways to produced a multitude of molecules. Therefore, PlastiCure has been think to be derived so we can use the plastic degradation of our system to produce a <b>huge diversity of products</b>. This make PlastiCure one of the <b>most innovative project</b>.</p></div>
 
  
 
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      <p style="text-indent:3em;"> We imagined creating interchangeable versions of each module. This would enable us to degrade a different plastic and still synthesize Erythromycin A or to degrade PET but synthesize a different molecule. Therefore, PlastiCure has been thought to be derived so we can use the plastic degradation module of our system to produce a <b>broad diversity of products</b>. This makes PlastiCure a <b>very flexible and innovative project</b>.</p></div>
 
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</br>
 
</br>
  <font size=2><p><b>References</b></p>
 
  <p><b>1</b> - <a href="https://static.igem.org/mediawiki/2015/e/ef/IGEM_Pasteur_Plastics_the_Facts_2014.pdf"> Plastics – the Facts 2014. An analysis of European plastics production, demand and waste data</a></p>
 
  <p><b>2</b> - <a href="http://www.planetoscope.com/petrole/989-production-mondiale-de-plastique.html">http://www.planetoscope.com/petrole/989-production-mondiale-de-plastique</a></p>
 
  <p><b>3</b> - <a href="https://static.igem.org/mediawiki/2015/e/ef/IGEM_Pasteur_Plastics_the_Facts_2014.pdf"> Plastics – the Facts 2014. An analysis of European plastics production, demand and waste data</a></p>
 
  <p><b>4</b> - <a href="http://app.dumpark.com/seas-of-plastic-2/#oceans">http://app.dumpark.com/seas-of-plastic-2/#oceans</a></p>
 
  <p><b>5</b> - <a href="http://erythromycin.org/erythromycin">http://erythromycin.org/erythromycin</a></p>
 
  <p><b>6</b> - <a href="https://en.wikipedia.org/wiki/Erythromycin#/media/File:Erythromycin_A.svg">https://en.wikipedia.org/wiki/File:Erythromycin_A.svg</a></p></font>
 
 
</br>
 
</br>
  
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        <font size=2><p><b>References</b></p>
  
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  <p><b>1</b> - <a href="https://static.igem.org/mediawiki/2015/e/ef/IGEM_Pasteur_Plastics_the_Facts_2014.pdf" style="text-decoration:none; color:#000000;" target="_blank"> Plastics – the Facts 2014. An analysis of European plastics production, demand and waste data</a></p>
 +
  <p><b>2</b> - <a href="http://www.planetoscope.com/petrole/989-production-mondiale-de-plastique.html" style="text-decoration:none; color:#000000;" target="_blank">http://www.planetoscope.com/petrole/989-production-mondiale-de-plastique</a></p>
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  <p><b>3</b> - <a href="https://static.igem.org/mediawiki/2015/e/ef/IGEM_Pasteur_Plastics_the_Facts_2014.pdf" style="text-decoration:none; color:#000000;" target="_blank"> Plastics – the Facts 2014. An analysis of European plastics production, demand and waste data</a></p>
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  <p><b>4</b> - <a href="http://app.dumpark.com/seas-of-plastic-2/#oceans" style="text-decoration:none; color:#000000;" target="_blank">http://app.dumpark.com/seas-of-plastic-2/#oceans</a></p>
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  <p><b>5</b> - <a href="https://www.youtube.com/watch?v=mGzIz9Ld-sE" style="text-decoration:none; color:#000000;" target="_blank">https://www.youtube.com/Plankton-eating-plastic</a></p>
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  <p><b>6</b> - <a href="http://erythromycin.org/erythromycin" style="text-decoration:none; color:#000000;" target="_blank">http://erythromycin.org/erythromycin</a></p>
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  <p><b>7</b> - Haoran Zhang, Yong Wang, Jiequn Wu, Karin Skalina, and Blaine A. Pfeifer (2010).</br> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Complete Biosynthesis of Erythromycin A and Designed Analogs Using <i>E. coli</i> as a Heterologous Host. </br>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Chemistry & Biology <i>17</i>, 1232–1240.</p>
 +
  <p><b>8</b> - <a href="https://en.wikipedia.org/wiki/Erythromycin#/media/File:Erythromycin_A.svg" style="text-decoration:none; color:#000000;" target="_blank">https://en.wikipedia.org/wiki/File:Erythromycin_A.svg</a></p></font></div>
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Latest revision as of 17:10, 11 November 2015




The Problem

Every year, more and more plastics are produced. In 2000, the world plastic production was about 190 million tons per year whereas today, it is roughly 300 million tons per year (Fig.1). The most common plastics are polyethylene (PE), polyethylene terephthalate (PET) and polypropylene (PP).

Fig.1 - Evolution of the world plastic production, in million of tons, from 1950 to 2020.1


However, the treatment of plastic is not yet suited to the exponential growth of plastic production. In 2012, Europe produced 25.2 million tons of plastic waste2, among which only 26% were recycled. The remaining 74% were either burned in order to produce energy (36%) or dumped and buried (38%). This leads to an increase in plastic in nature which pollutes our ecosystem, especially the oceans.

Fig.2 - Treatment of post-consumer plastics waste in 2012, in the European Union.3


The problem is worsened by the size of the plastic particles: they are mostly microparticles. Indeed, over 90% of the ocean’s plastic particles measure less than 5mm. This makes it difficult to clean the plastic out of the ocean. The greatest danger comes from invisible plastic since the particles are becoming small enough to be accidentally ingested by zooplankton.4 Indeed, oxidation and UV radiation can break the plastic into small fragments which can attain a minimum size of 20µm. The plastic then works its way up our food chain and ends up on our plates.5






Our solution

PlastiCure is a biological system designed to degrade PET and use the degradation products to synthesize bio-active compounds. The idea is to create a new way to treat plastic waste by degrading it into a novel profitable transformation product and then increase efforts in plastic recycling.


The challenge of the project is to combine in one system a PET degradation pathway with an optimized biosynthetic pathway: we aim to transform plastic waste into a profitable life-saving drug, erythromycin A. This constitutes a revalorisation of plastic waste into drug. E. coli will be used as a heterologous host to integrate exogenous DNA sequences in multiple operons (82 % of our designed operons will be composed of heterologous genes). This will allow E. coli to express all of the necessary biodegradation and biosynthesis genes.


Fig.3 - Our E. coli system is able to synthesize biologically active products and at the same time degrade plastic waste.


Erythromycin is an antibiotic used to treat bacterial infections in cases of allergy to penicillin. It is hence a frequently prescribed drug. Erythromycin also has an important role in the hemi synthesis of new active ingredients. Despite a very important demand, the total synthesis of erythromycin A remains a very long and complex process of about 50 stages. It is therefore an expensive process.6


Recent advances in synthetic biology enabled erythromycin production in E. coli. B. Pfeifer and H. Zhang designed a system of 4 plasmids working in the E. coli BAP 1 strain and leading to erythromycin A production with a yield of 10 mg per liter of culture media.7

Fig.4 - The very complex molecule of erythromycin A.8


PlastiCure is a well-designed biological system composed of 2 parts: degradation and synthesis. The PET degradation part is composed of 2 pathways: terephthalic acid (green arrows) and ethylene glycol (blue arrows). In total, the two pathways are composed of 15 genes (~22 kb), that will be integrated in an operon into one plasmid.


Fig.5 - Degradation pathway of the system.


Erythromycin A is synthesized by a modular Polyketide Synthase (type 1). The products of degradation, propionyl-CoA and (S)-Methylmalonyl-CoA, are used to synthesize 6-deoxyerythronolide B (6deB). Ery operon enzymes will make erythromycin A using 6deB as a precursor.


Fig.6 - Propionate metabolism in E. coli BAP 1.


We imagined creating interchangeable versions of each module. This would enable us to degrade a different plastic and still synthesize Erythromycin A or to degrade PET but synthesize a different molecule. Therefore, PlastiCure has been thought to be derived so we can use the plastic degradation module of our system to produce a broad diversity of products. This makes PlastiCure a very flexible and innovative project.



References

1 - Plastics – the Facts 2014. An analysis of European plastics production, demand and waste data

2 - http://www.planetoscope.com/petrole/989-production-mondiale-de-plastique

3 - Plastics – the Facts 2014. An analysis of European plastics production, demand and waste data

4 - http://app.dumpark.com/seas-of-plastic-2/#oceans

5 - https://www.youtube.com/Plankton-eating-plastic

6 - http://erythromycin.org/erythromycin

7 - Haoran Zhang, Yong Wang, Jiequn Wu, Karin Skalina, and Blaine A. Pfeifer (2010).
      Complete Biosynthesis of Erythromycin A and Designed Analogs Using E. coli as a Heterologous Host.
      Chemistry & Biology 17, 1232–1240.

8 - https://en.wikipedia.org/wiki/File:Erythromycin_A.svg



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