Plasmodium heme biosynthesis: To be or not to be essential?

Sequencing of the Plasmodium falciparum genome in 2002 sparked hopes that metabolic pathway annotation could identify new parasite-specific targets for therapeutic intervention [1]. Cashing in on this potential has proved challenging because many pathways have unexpected properties and/or are only required in certain host environments. Heme biosynthesis has been considered as a possible antimalarial target. Our understanding of heme acquisition mechanisms and the role of heme biosynthesis in different stages of Plasmodium parasite development has evolved considerably in recent years. In this Pearl, we summarize recent major findings and highlight remaining questions.