Difference between revisions of "Team:UCSC/Acetaminophen"

Line 1: Line 1:
 
{{UCSC-Header}}
 
{{UCSC-Header}}
 
 
<html>
 
<html>
 
 
<style>
 
<style>
 
 
.metabolic-pathway {
 
.metabolic-pathway {
 
   margin: auto;
 
   margin: auto;
Line 10: Line 7:
 
   width: 85%;
 
   width: 85%;
 
}
 
}
 
 
h1 {
 
h1 {
 
   font-family: "Objektiv-mk1"!important;
 
   font-family: "Objektiv-mk1"!important;
Line 16: Line 12:
 
   font-size: 400%; /*!important*/
 
   font-size: 400%; /*!important*/
 
}
 
}
 
 
#page {
 
#page {
 
   background: honeydew;
 
   background: honeydew;
Line 356: Line 351:
 
<div class="quote-person"> ~Clinical Manual of Fever in Children</div>
 
<div class="quote-person"> ~Clinical Manual of Fever in Children</div>
 
</div>
 
</div>
 
 
<br>
 
<br>
<br>
 
<br>
 
 
 
<div class="metabolic-pathway">
 
<div class="metabolic-pathway">
 
<img src="https://static.igem.org/mediawiki/2017/0/02/Ace_pathway.png" style="width: 75%;">
 
<img src="https://static.igem.org/mediawiki/2017/0/02/Ace_pathway.png" style="width: 75%;">
 
</div>
 
</div>
 
 
<br>
 
<br>
<br>
 
 
 
<div class="text-container">
 
<div class="text-container">
 
<div class="paragraph-left">
 
<div class="paragraph-left">
We aim to genetically modify PCC 7942 to produce acetaminophen, a common mild anesthetic and antipyretic recognized by the WHO as an essential medicine <sup>[1]</sup>. However, in many countries with lower regulations and faulty policies regarding drug manufacturing, acetaminophen can be synthesized with lethal toxins that result in hundreds of deaths worldwide <sup>[23]</sup>.  Acetaminophen is oftenused in conjunction with opioid pain medications postoperatively to enhance pain relief, thus reducing reliance upon opioid pharmaceuticals <sup>[24]</sup>.
+
We aim to genetically modify cyanobacteria <i>Synechococcus elongatus PCC 7942</i> to produce acetaminophen, also called paracetamol, a common anesthetic and antipyretic recognized by the WHO as an essential medicine <sup>[1]</sup>. The active ingredient in Tylenol, acetaminophen works synergistically with opioid pain medications to enhance pain relief,  reducing costs and reliance upon addictive opioid pharmaceuticals <sup>[24]</sup>. In some countries with lower regulations on drug manufacturing, acetaminophen has been synthesized with lethal toxins that has resulted in hundreds of deaths worldwide <sup>[23]</sup>.  Our modified organism will provide consistent, sustainable medicine, ensuring that anyone with sunlight, fertilizer, and water will be able to produce their own supply of acetaminophen.
 
</div>
 
</div>
 
</div>
 
</div>
Line 394: Line 382:
 
<figure>
 
<figure>
 
<img src="https://static.igem.org/mediawiki/2017/7/79/Pathway_%281%29.png" style="width: 100%;">
 
<img src="https://static.igem.org/mediawiki/2017/7/79/Pathway_%281%29.png" style="width: 100%;">
<figcaption>Current  synthetic  biology  approach  to  manufacturing  acetaminophen  in  <span style="font-style: italic";>E. coli</span> <sup>[25, 26]</sup>. Genes <span style="font-style: italic";>4ABH</span> and <span style="font-style: italic";>nhoA</span>  were  inserted  to  synthesize  the  pathway  in  PCC  7942. The  gene  from  <span style="font-style: italic";>A. bisporus, 4ABH</span>, produces 4-aminophenol while the <span style="font-style: italic";>E. coli</span> gene <span style="font-style: italic";>nhoA</span> converts that 4-aminophenol to acetaminophen <sup>[25]</sup>.</figcaption>
+
<figcaption>Current  synthetic  biology  approach  to  manufacturing  acetaminophen  in  <i>E. coli</i> <sup>[25, 26]</sup>. Genes <i>4ABH</i> and <i>NhoA</i>  were  inserted  to  synthesize  the  pathway  in  PCC  7942. The  gene  from  <i>A. bisporus, 4ABH</i>, produces 4-aminophenol while the <span style="font-style: italic";>E. coli</span> gene <span style="font-style: italic";>NhoA</span> converts that 4-aminophenol to acetaminophen <sup>[25]</sup>.</figcaption>
 
</figure>
 
</figure>
 
</div>
 
</div>

Revision as of 01:29, 6 October 2017


Acetaminophen Metabolics

"Antipyretic drugs, by being analgesics, reduce not only the fever but also the pain."

~Clinical Manual of Fever in Children


We aim to genetically modify cyanobacteria Synechococcus elongatus PCC 7942 to produce acetaminophen, also called paracetamol, a common anesthetic and antipyretic recognized by the WHO as an essential medicine [1]. The active ingredient in Tylenol, acetaminophen works synergistically with opioid pain medications to enhance pain relief, reducing costs and reliance upon addictive opioid pharmaceuticals [24]. In some countries with lower regulations on drug manufacturing, acetaminophen has been synthesized with lethal toxins that has resulted in hundreds of deaths worldwide [23]. Our modified organism will provide consistent, sustainable medicine, ensuring that anyone with sunlight, fertilizer, and water will be able to produce their own supply of acetaminophen.
Current synthetic biology approach to manufacturing acetaminophen in E. coli [25, 26]. Genes 4ABH and NhoA were inserted to synthesize the pathway in PCC 7942. The gene from A. bisporus, 4ABH, produces 4-aminophenol while the E. coli gene NhoA converts that 4-aminophenol to acetaminophen [25].




We are using a previously engineered pathway in E. coli as a model of acetaminophen biosynthesis to enhance PCC 7942 [26, 25]. The pathway converts chorismate, an abundant aminoacid precursor of tryptophan, phenylalanine, and tyrosine, into acetaminophen with the addition ofthe 4ABH gene from A. bisporus, an edible mushroom, and nhoA from E. coli.




  • [1] World Health Organization, ed.,The Selection and Use of Essential Medicines: report of theWHO Expert Committee, 2007 ; (including the 15th model list of essential medicines). No. 946in WHO Technical Report Series, Geneva: World Health Organization, 2007. OCLC: 254437808.
  • [23] P. N. Newton, M. D. Green, and F. M. Fern ́andez, “Impact of poor-quality medicines in the‘developing’ world,”Trends in Pharmacological Sciences, vol. 31, pp. 99–101, Mar. 2010.
  • [24] S. A. Schug, D. A. Sidebotham, M. McGuinnety, J. Thomas, and L. Fox, “Acetaminophen as anadjunct to morphine by patient-controlled analgesia in the management of acute postoperativepain,”Anesthesia and Analgesia, vol. 87, pp. 368–372, Aug. 1998.
  • [25] A. A. Menezes, J. Cumbers, J. A. Hogan, and A. P. Arkin, “Towards synthetic biological ap-proaches to resource utilization on space missions,”Journal of the Royal Society, Interface, vol. 12,p. 20140715, Jan. 2015.
  • [26] J. C. Anderson, T. HSIAU, S. Srivastava, P. RUAN, J. P. I. KOTKER, R. BODIK, and S. A.Seshia, “Method for biosynthesis of acetaminophen,” May 2016. International ClassificationC12P13/02, C12N1/21; Cooperative Classification C12N9/1029, C12N9/0073, C12P13/02.