Plasmodium falciparum COQ2 gene encodes a functional 4-hydroxybenzoate polyprenyltransferase.

Ubiquinone is a fundamental mitochondrial electron transport chain component. This compound is synthesized as the condensation of a p-substituted benzoic acid and a polyisoprenic moiety catalyzed by the enzyme 4-hydroxybenzoate polyprenyltransferase (EC 2.5.1.39). In Plasmodium spp., this enzyme is still uncharacterized. In this work, we expressed the sequence of the Plasmodium falciparum PF3D7_0607500 gene (abbreviated as PfCOQ2) in a coq2Δ mutant strain of Saccharomyces cerevisiae, and studied the functionality of its gene product. This open reading frame could complement S. cerevisiae coq2Δ mutant growth defect on media with glycerol as a carbon source. Further, ubiquinone was unequivocally identified in lipid extracts from this coq2Δ mutant when expressing PfCOQ2. Remarkably, ubiquinone was detected under those conditions when S. cerevisiae cells were metabolically labeled with either [ring-14C(U)]-p-aminobenzoic acid or [ring-14C(U)]-4-hydroxybenzoic acid. However, no ubiquinone was detected in P. falciparum if labeled with p-aminobenzoic acid. These results indicate that PfCOQ2 is a 4-hydroxybenzoate polyprenyltransferase. Further, its substrate profile seems not dissimilar to that of S. cerevisiae, but, as in other organisms, p-aminobenzoic acid does not act as an aromatic precursor in ubiquinone biosynthesis in P. falciparum. The reason for this last feature remains to be established, but may lie upstream of PfCOQ2.