Difference between revisions of "Team:UCSC/Acetaminophen"

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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.
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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 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.
 
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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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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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Revision as of 02:09, 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 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.