Plasmodium falciparum COQ2 gene encodes a functional 4-hydroxybenzoate polyprenyltransferase

Autor(es)

Zafra, Camila Andrea ; Crispim, Marcell ; Verdaguer, Ignasi Bofill ; Rios, Alejandro Garcia ; Moura, Gabriel Candido ; Katzin, Alejandro Miguel ; Hernandez, Agustin

• Tipo de documento: Artigo Científico
• Fonte: FEMS Microbiology Letters; v. 370, p. 8-pg., 2023-01-17.

Resumo

The malaria parasite first enzyme in the ubiquinol biosynthesis pathway, Coq2, could use pABA or 4-HB as a substrate, like yeasts do, but, in vivo, the parasite only uses 4-HB. Ubiquinone (UQ) 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 coq2 & UDelta; mutant strain of Saccharomyces cerevisiae, and studied the functionality of its gene product. This open reading frame could complement S. cerevisiae coq2 & UDelta; mutant growth defect on media with glycerol as a carbon source. Further, UQ was unequivocally identified in lipid extracts from this coq2 & UDelta; mutant when expressing PfCOQ2. Remarkably, UQ was detected under those conditions when S. cerevisiae cells were metabolically labeled with either [ring-C-14(U)]-p-aminobenzoic acid or [ring-C-14(U)]-4-hydroxybenzoic acid. However, no UQ 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 UQ biosynthesis in P. falciparum. The reason for this last feature remains to be established, but may lie upstream of PfCOQ2. (AU)

• Processo FAPESP: 19/04579-0 - Avaliação da 4-hidroxibenzoato polipreniltranferase de Plasmodium falciparum (PfUbiA) na biossíntese de ubiquinonas
• Beneficiário: Camila Andrea Zafra Alba
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/22452-1 - Biossíntese de isoprenóides em Plasmodium falciparum: avaliação de possíveis alvos para a obtenção de novas drogas antimaláricas
• Beneficiário: Alejandro Miguel Katzin
• Modalidade de apoio: Auxílio à Pesquisa - Temático