Garg, Varun (University of Utah)
Faculty Advisor: Balagurunathan, Kuberan (University of Utah, College of Pharmacy; Medicinal Chemistry)
Heparin is a widely-used blood anticoagulant medicine that is used in surgeries and in treatment of circulatory system illnesses. Heparin is currently harvested from live pigs before they are slaughtered. There are many problems with the current production process of heparin. On a chemical level, the drug can be easily and accidentally altered due to its complex chemical nature. In addition, the environmental impact of the pigs that need to be raised on farms and fed is immense. These reasons and more are why bioengineering approaches towards the artificial synthesis of Heparin need to be researched. One of the major obstacles in the synthesis of heparin is the production of Low Molecular Weight (LMW) Heparosan, a chemical precursor. The research goal is to find methods to increase LMW Heparosan yields to a point where those same yields can be used to conduct further exploration into Heparosan oligosaccharide precursors. These oligosaccharides are useful in further understanding heparin structure-function relationships and will eventually help in the goal to find a commercially viable, cost and time effective method of heparin production. Using shake flask bacterial cultures, LMW Heparosan was produced while adjusting variables such as bacterial density at induction and incubation time to maximize yield. Once a sufficient yield was obtained, oligosaccharide structures spliced from the LMW Heparosan were classified for further research. The initial shake flask experiments showed increased yield and purity of Heparosan for each successive trial. Further work is required to scale up production of LMW Heparosan to a mass-market synthetic Heparin but the research conducted shows a promising method to synthesize and improve yields to make that possible.