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

John G. Mina, Julie K. Thye, Amjed Q. I. Alqaisi, Louise E. Bird, Robert H. Dods, Morten K. Groftehauge, Jackie A. Mosely, Steven Pratt, Hosam Shams-Eldin, Ralph T. Schwarz, Ehmke Pohl, Paul W. Denny

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    Abstract

    Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation, and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis: the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote.
    Original languageEnglish
    Pages (from-to)12208-12219
    Number of pages12
    JournalJournal of Biological Chemistry
    Volume292
    Issue number29
    Early online date2 Jun 2017
    DOIs
    Publication statusPublished - 21 Jul 2017

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    Mina, J. G., Thye, J. K., Alqaisi, A. Q. I., Bird, L. E., Dods, R. H., Groftehauge, M. K., Mosely, J. A., Pratt, S., Shams-Eldin, H., Schwarz, R. T., Pohl, E., & Denny, P. W. (2017). Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites. Journal of Biological Chemistry, 292(29), 12208-12219. https://doi.org/10.1074/jbc.M117.792374