"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!

  • [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.