Difference between revisions of "Team:Tel-Hai/Model"

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<h1>Modeling</h1>
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<h2>The model of resveratrol biosynthesis</h2>
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<h3>Resveratrol is an antioxidant found predominantly in the peel of the grapes, and is a part of the plant’s antibacterial and antifungal defense. Resveratrol is one of the components of red wine which are beneficial to human health.</h3>
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<p>Research has shown that it improves cardiovascular health and affects, among other things, various factors of cellular ageing. Our vision for Wonder Wine is that it should encapsulate a multitude of beneficial attributes, primarily health-related. </p>
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<p>Recently, advancement has been achieved in creating engineered yeast which contained two foreign enzymes essential to resveratrol biosynthesis1. These enzymes, originally found in grapes, are 4CL (P-coumarate-CoA ligase) and RS (Resveratrol Synthase). 4CL turns p-coumarate into p-coumaroyl-CoA, which is then used by RS to produce resveratrol. Since p-coumarate is not found naturally in yeast, the scientists RS had to add it to the medium in order for resveratrol synthesis to occur. That's where we come in. We would like to demonstrate, with the help of a model, how the introduction of a third enzyme from grapes – TAL (Tyrosine-Ammonia-Lyase) can obviate the need to supply p-coumarate externally. TAL can convert L-tyrosine, found naturally in yeast, into p-coumarate, thereby supplying the missing building block for resveratrol biosynthesis, with no need for specialized media. </p>
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<p>Our model is meant to predict the overall success (or otherwise) of the yeast resveratrol pathway with the addition of TAL (Fig. 1). It was created by using Copasi2 – a software for the simulation of biochemical networks, which implements MCA – metabolic control analysis. MCA is a comprehensive mathematical framework invented to deal with the response of metabolic pathways, at steady state, to small perturbations in the activity of enzymes and the concentrations of the various metabolites. It can calculate the steady-state flux through the pathway, the control coefficients of the participating enzymes and the steady-state concentration of each metabolite.</p>
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<p>The model includes four enzymes (in this order):</p>
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<p>PAH - Phenylalanine hydroxylase(E.C 1.14.16.1)</p>
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<p>The reaction: </p>
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<p>L-phenylalanine + BH4 + O2  L-tyrosine + 4-hydroxy-BH4</p>
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<p>Rate equation: </p>
  
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<p>**T--Tel-Hai—PAH**</p>
  
<h3>★  ALERT! </h3>
 
<p>This page is used by the judges to evaluate your team for the <a href="https://2017.igem.org/Judging/Medals">medal criterion</a> or <a href="https://2017.igem.org/Judging/Awards"> award listed above</a>. </p>
 
<p> Delete this box in order to be evaluated for this medal criterion and/or award. See more information at <a href="https://2017.igem.org/Judging/Pages_for_Awards"> Instructions for Pages for awards</a>.</p>
 
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<p>TAL-Tyrosine-Ammonia-Lyase (EC 4.3.1.23)</p>
<h1> Modeling</h1>
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<p>The reaction: </p>
 
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<p>L-tyrosine p-coumaric acid+NH3+H </p>
<p>Mathematical models and computer simulations provide a great way to describe the function and operation of BioBrick Parts and Devices. Synthetic Biology is an engineering discipline, and part of engineering is simulation and modeling to determine the behavior of your design before you build it. Designing and simulating can be iterated many times in a computer before moving to the lab. This award is for teams who build a model of their system and use it to inform system design or simulate expected behavior in conjunction with experiments in the wetlab.</p>
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<p>Rate equation: </p>
 
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<p>**T--Tel-Hai—TAL**</p>
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<h3> Gold Medal Criterion #3</h3>
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To complete for the gold medal criterion #3, please describe your work on this page and fill out the description on your <a href="https://2017.igem.org/Judging/Judging_Form">judging form</a>. To achieve this medal criterion, you must convince the judges that your team has gained insight into your project from modeling. You may not convince the judges if your model does not have an effect on your project design or implementation.
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Please see the <a href="https://2017.igem.org/Judging/Medals"> 2017 Medals Page</a> for more information.
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<h3>Best Model Special Prize</h3>
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To compete for the <a href="https://2017.igem.org/Judging/Awards">Best Model prize</a>, please describe your work on this page  and also fill out the description on the <a href="https://2017.igem.org/Judging/Judging_Form">judging form</a>. Please note you can compete for both the gold medal criterion #3 and the best model prize with this page.
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<br><br>
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You must also delete the message box on the top of this page to be eligible for the Best Model Prize.
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<h5> Inspiration </h5>
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Here are a few examples from previous teams:
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<ul>
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<li><a href="https://2016.igem.org/Team:Manchester/Model">Manchester 2016</a></li>
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<li><a href="https://2016.igem.org/Team:TU_Delft/Model">TU Delft 2016  </li>
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<li><a href="https://2014.igem.org/Team:ETH_Zurich/modeling/overview">ETH Zurich 2014</a></li>
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<li><a href="https://2014.igem.org/Team:Waterloo/Math_Book">Waterloo 2014</a></li>
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<p>4CL - P-coumarate-CoA ligase (EC 6.2.1.12)</p>
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<p>The reaction:</p>
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<p>ATP+p-coumarat+CoA  AMP+diphosphate+p-coumaroyl-CoA</p>
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<p>Rate equation: </p>
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<p>**T--Tel-Hai--4CL**</p>
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{{Tel-Hai/footer}}

Revision as of 16:39, 31 October 2017

Modeling

The model of resveratrol biosynthesis

Resveratrol is an antioxidant found predominantly in the peel of the grapes, and is a part of the plant’s antibacterial and antifungal defense. Resveratrol is one of the components of red wine which are beneficial to human health.

Research has shown that it improves cardiovascular health and affects, among other things, various factors of cellular ageing. Our vision for Wonder Wine is that it should encapsulate a multitude of beneficial attributes, primarily health-related.

Recently, advancement has been achieved in creating engineered yeast which contained two foreign enzymes essential to resveratrol biosynthesis1. These enzymes, originally found in grapes, are 4CL (P-coumarate-CoA ligase) and RS (Resveratrol Synthase). 4CL turns p-coumarate into p-coumaroyl-CoA, which is then used by RS to produce resveratrol. Since p-coumarate is not found naturally in yeast, the scientists RS had to add it to the medium in order for resveratrol synthesis to occur. That's where we come in. We would like to demonstrate, with the help of a model, how the introduction of a third enzyme from grapes – TAL (Tyrosine-Ammonia-Lyase) can obviate the need to supply p-coumarate externally. TAL can convert L-tyrosine, found naturally in yeast, into p-coumarate, thereby supplying the missing building block for resveratrol biosynthesis, with no need for specialized media.

Our model is meant to predict the overall success (or otherwise) of the yeast resveratrol pathway with the addition of TAL (Fig. 1). It was created by using Copasi2 – a software for the simulation of biochemical networks, which implements MCA – metabolic control analysis. MCA is a comprehensive mathematical framework invented to deal with the response of metabolic pathways, at steady state, to small perturbations in the activity of enzymes and the concentrations of the various metabolites. It can calculate the steady-state flux through the pathway, the control coefficients of the participating enzymes and the steady-state concentration of each metabolite.

The model includes four enzymes (in this order):

PAH - Phenylalanine hydroxylase(E.C 1.14.16.1)

The reaction:

L-phenylalanine + BH4 + O2  L-tyrosine + 4-hydroxy-BH4

Rate equation:

**T--Tel-Hai—PAH**

TAL-Tyrosine-Ammonia-Lyase (EC 4.3.1.23)

The reaction:

L-tyrosine p-coumaric acid+NH3+H

Rate equation:

**T--Tel-Hai—TAL**

4CL - P-coumarate-CoA ligase (EC 6.2.1.12)

The reaction:

ATP+p-coumarat+CoA  AMP+diphosphate+p-coumaroyl-CoA

Rate equation:

**T--Tel-Hai--4CL**