Determining the Biosynthetic Pathway of Rhodoquinone in C. elegans

Abstract

Parasitic helminths infect more than 1.5 billion people, with third world countries being the most affected. Parasites are transmitted through soil and contaminated water and they feed on host tissue in order to grow and reproduce. Infections cause anemia, malabsorption of nutrients, and loss of appetite. While inside a host, parasites anaerobically respire by using an alternative electron transport chain that uses rhodoquinone (RQ) as an electron carrier instead of ubiquinone (Q), which is used in aerobic respiration. Mammalian hosts produce and use Q for aerobic respiration, but they do not make or require RQ. An ideal anti‐parasitic drug target would be an enzyme that is used only for the biosynthesis of RQ ‐ not the biosynthesis of Q. Caenorhabditis elegans have been used as a model system for parasitic helminths in order to investigate RQ biosynthesis. RNAi feeding experiments were performed to identify genes required for several steps in the RQ biosynthetic pathway in C. elegans. Several genes were identified that are common to both Q and RQ biosynthetic pathways (coq‐3, coq‐5, and coq‐6). However, knockdown of the kynu‐1 gene from the kynurenine pathway affected only RQ production. Additional experiments involving knock‐outs of other C. elegans genes in the kynurenine pathway confirmed the requirement of kynu‐1 and the corresponding arylamine products for the biosynthesis of RQ. The roles ofcoq‐2 and coq‐3 MV genes in the biosynthesis of RQ in C. elegans were further investigated in this study using RNAi knockdowns and characterization was performed with RT‐qPCR and LC‐MS.Support or Funding InformationGonzaga Science Research Program and Agencia Nacional para la Innovación y la Investigación ANII FCE_1_2014_104366