The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Interestingly, co-occurrence of polyprenols and dolichols, i.e. detection of a dolichol along with significant levels of its precursor polyprenol, are unusual in eukaryotic cells. Our metabolomics studies revealed that cis-polyisoprenoids are more diverse in the malaria parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite’s development. Moreover, we confirmed the presence of an active cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (AI108819 to M.B.C.) and American Heart Association Postdoctoral Fellowship (18POST34080315 to A.F.). The following reagents were obtained through MR4 as part of the BEI Resources Repository, NIAID, NIH: P. falciparum, strain NF54 (MRA-1000), contributed by M. Dowler, Walter Reed Army Institute of research and strain 3D7 (MRA-102) contributed by Daniel J. Carucci. We thank Julie Nelson for providing access to CTEGD flow cytometry core facility and Muthugapatti Kandasamy at the Biomedical Microscopy Core at the University of Georgia for help with microscopy. We thank Dennis Kyle for the gift of [3-13C]IPP. The yeast strains were kindly supplied to E.S. by Vincent Cantagrel. We thank Grant Butschek for comments and corrections.
© 2020, The Author(s).