Hannah D'Ambrosio, Ph.D. Candidate
Emily Derbyshire, Ph.D., Advisor
Abstract: The apicomplexan parasite Toxoplasma gondii is one of the most highly distributed parasites on earth. Despite this, little is known about the chemical mechanisms utilized by the parasite during the stages of its complex life cycle. Although protists are not traditionally a significant area in natural product research, T. gondii possess multiple putative polyketide synthase (PKS) biosynthetic gene clusters, indicating their potential to be a unique source of undiscovered secondary metabolites. To date, there have been no characterized PKS enzymes or natural product metabolites from any apicomplexan parasite, leaving this potentially rich area unexplored. Utilizing biochemical, bioinformatic, and molecular tools, we have uncovered unique enzymatic features of PKS domains from T. gondii, while revealing structural information about the uncharacterized polyketide metabolite. We have additionally begun to expose the role theses mega-enzymes play in the complex biology of theses parasites, laying the groundwork for further exploration into natural product biosynthesis in Apicomplexa.