Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites

Toxoplasma gondiiis an obligate, intracellular eukaryoticapicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipidsare essential and ubiquitous components of eukaryoticmembranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation and analyses of the Toxoplasma serinepalmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipidbiosynthesis - the condensation of serineand palmitoyl-CoA. In all eukaryotesanalyzed to date, serinepalmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serinepalmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serinepalmitoyltransferase, identified in the Sphingomonadaceaeas a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. Importantly, the structural and evolutionary divergence of the apicomplexan serinepalmitoyltransferase suggests that it might have significant potential as a drug target.