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<h1>ACETAMINOPHEN METABOLICS</h1>
  
 
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<p>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>.</p>
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<p>We aim to genetically modify <i>S. elongatus</i> 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 often used in conjunction with opioid pain medications postoperatively to enhance pain relief, thus reducing reliance upon opioid pharmaceuticals<sup>[24]</sup>.</p>
 
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<figcaption style="font-family: 'objektiv-mk1'; font-style: italic; font-size: 13px;">Current  synthetic  biology  approach  to  manufacturing  acetaminophen  in  E.coli  <sup>[25, 26]</sup>.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 <sup>[25]</sup>.</figcaption>
 
<figcaption style="font-family: 'objektiv-mk1'; font-style: italic; font-size: 13px;">Current  synthetic  biology  approach  to  manufacturing  acetaminophen  in  E.coli  <sup>[25, 26]</sup>.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 <sup>[25]</sup>.</figcaption>
 
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<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  <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>
 
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We are using a previously engineered pathway in <span style="font-style: italic";>E. coli</span> as a model of acetaminophen biosynthesis to enhance PCC 7942 <sup>[26, 25]</sup>. The pathway converts chorismate, an abundant aminoacid precursor of tryptophan, phenylalanine, and tyrosine, into acetaminophen with the addition ofthe <span style="font-style: italic";>4ABH</span> gene from <span style="font-style: italic";>A. bisporus</span>, an edible mushroom, and <span style="font-style: italic";>nhoA</span> from <span style="font-style: italic";>E. coli</span>.
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<p>We are using a previously engineered pathway in <span style="font-style: italic";>E. coli</span> as a model of acetaminophen biosynthesis to enhance PCC 7942<sup>[26, 25]</sup>. The pathway converts chorismate, an abundant amino acid precursor of tryptophan, phenylalanine, and tyrosine, into acetaminophen with the addition ofthe <span style="font-style: italic";>4ABH</span> gene from <span style="font-style: italic";>A. bisporus</span>, an edible mushroom, and <span style="font-style: italic";>nhoA</span> from <span style="font-style: italic";>E. coli</span>. For more information on acetaminophen metabolics, check out <a href="https://2017.igem.org/Team:UCSC/Model">our modeling page!</a></p>
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<h3>P R O J E C T</h3>
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<li>[1] World  Health  Organization,  ed.,<span class="reference-italic">The  Selection  and  Use  of  Essential  Medicines:  report  of  theWHO Expert  Committee,  2007  ;  (including  the  15th  model  list  of  essential  medicines).</span>  No. 946in WHO Technical Report Series, Geneva:  World Health Organization, 2007. OCLC: 254437808.</li>
+
<li>[1] World  Health  Organization,  ed.,<span class="reference-italic">The  Selection  and  Use  of  Essential  Medicines:  report  of  the WHO Expert  Committee,  2007  ;  (including  the  15th  model  list  of  essential  medicines).</span>  No. 946in WHO Technical Report Series, Geneva:  World Health Organization, 2007. OCLC: 254437808.</li>
 
<li>[23] P.  N.  Newton,  M.  D.  Green,  and  F.  M.  Fern ́andez,  “Impact  of  poor-quality  medicines  in  the‘developing’ world,”<span class="reference-italic">Trends in Pharmacological Sciences</span>, vol. 31, pp. 99–101, Mar. 2010.</li>
 
<li>[23] P.  N.  Newton,  M.  D.  Green,  and  F.  M.  Fern ́andez,  “Impact  of  poor-quality  medicines  in  the‘developing’ world,”<span class="reference-italic">Trends in Pharmacological Sciences</span>, vol. 31, pp. 99–101, Mar. 2010.</li>
 
<li>[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,”<span class="reference-italic">Anesthesia and Analgesia</span>, vol. 87, pp. 368–372, Aug. 1998.</li>
 
<li>[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,”<span class="reference-italic">Anesthesia and Analgesia</span>, vol. 87, pp. 368–372, Aug. 1998.</li>
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Latest revision as of 01:44, 2 November 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 S. elongatus PCC 7942 to produce acetaminophen, a common mild anesthetic and antipyretic recognized by the WHO as an essential medicine[1]. 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[23]. Acetaminophen is often used in conjunction with opioid pain medications postoperatively to enhance pain relief, thus reducing reliance upon opioid pharmaceuticals[24].

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 amino acid 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. For more information on acetaminophen metabolics, check out our modeling page!




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  • [1] World Health Organization, ed.,The Selection and Use of Essential Medicines: report of the WHO 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.


    • S P O N S O R S
    S O C I A L
    C O N T A C T
    Jack Baskin School of Engineering
    University of California, Santa Cruz
    1156 High Street
    Santa Cruz, California, 95064