Plasmodium falciparum is the causative agent of the most severe form of human 
malaria. The rapid multiplication of the parasite within human erythrocytes 
requires an active production of new membranes. Phosphatidylcholine is the most 
abundant phospholipid in Plasmodium membranes, and the pathways leading to its 
synthesis are attractive targets for chemotherapy. In addition to its synthesis 
from choline, phosphatidylcholine is synthesized from serine via an unknown 
pathway. Serine, which is actively transported by Plasmodium from human serum 
and readily available in the parasite, is subsequently converted into 
phosphoethanolamine. Here, we describe in P. falciparum a plant-like 
S-adenosyl-l-methionine-dependent three-step methylation reaction that converts 
phosphoethanolamine into phosphocholine, a precursor for the synthesis of 
phosphatidylcholine. We have identified the gene, PfPMT, encoding this activity 
and shown that its product is an unusual phosphoethanolamine methyltransferase 
with no human homologs. P. falciparum phosphoethanolamine methyltransferase 
(Pfpmt) is a monopartite enzyme with a single catalytic domain that is 
responsible for the three-step methylation reaction. Interestingly, Pfpmt 
activity is inhibited by its product phosphocholine and by the phosphocholine 
analog, miltefosine. We show that miltefosine can also inhibit parasite 
proliferation within human erythrocytes. The importance of this enzyme in P. 
falciparum membrane biogenesis makes it a potential target for malaria 
chemotherapy.