Proteobacteria-like ferrochelatase in the malaria parasite.

A gene encoding the heme biosynthetic enzyme ferrochelatase (FC) was found in the genomic DNA databases of Plasmodium spp. The predicted amino acid sequence of malarial FC is highly conserved and fairly well conserved by comparison with other orthologues. The FC genes of P. falciparum and P. yoelii are transcribed and the mRNAs are processed to encode polypeptides of the expected amino acid sequence. The cloned cDNA for the FC of P. falciparum successfully rescued a FC-null mutant of Escherichia coli, indicating that it encodes an active enzyme. Unlike eukaryotic FCs, the malarial enzyme lacks a characteristic extension at the C-terminus. In addition, the sequence of the malarial FC resembles proteobacterial orthologues rather than eukaryotic enzymes. Strikingly, the malarial FC lacks a bipartite presequence at its N-terminus, unlike delta-aminolevulinic acid dehydratase of the same organism. This suggests an unusual intracellular distribution of heme biosynthetic enzymes, involving multiple subcellular compartments.