Study of prenylquinones aromatic origin in Plasmodium falciparum

• Grant number: 19/08634-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2019
• End date: March 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Alejandro Miguel Katzin
• Grantee: Gabriel Cândido Moura
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/22452-1 - Biosynthesis of isoprenoids in Plasmodium falciparum: evaluation of possible targets to obtain new anti-malarial drugs, AP.TEM

Abstract

Malaria is an infection disease caused by several species of Apicomplexa parasites of the genus Plasmodium. In 2017 Malaria affected 219 million people around the world and caused 435 thousand deaths, mostly by P. falciparum infections. Furthermore, to go up against the global emergence of drug resistance, new targets for drug development became necessary. Thereby, this work focuses on the study of the shikimate pathway: a 7-step pathway, which is present in plants, bacteria and fungi, as well as in Apicomplexa, but is absent in human and that produces chorismate, a key substrate to produce many prenylquinones. Prenylquinones have a structure composed of an isoprene chain derived from MEP pathway and an aromatic group from the shikimate pathway. However, as a type of prenylquinones, the ubiquinones an important role in the mitochondrial electron transport chain. The aromatic portion of these molecules is due to chorismate liase (gen UbiC) responsible for the formation of 4-hydroxybenzoate. Although our laboratory has studied much of the biosynthesis of isoprene chains of prenylquinones, it is also necessary to understand the origin of the aromatic that make up such molecules. (AU)