From B to A: making an essential cofactor in a human parasite.

Trypanosomatids are parasitic eukaryotic organisms that cause human disease. These organisms have complex lifestyles; cycling between vertebrate and insect hosts and alternating between two morphologies; a replicating form and an infective, nonreplicating one. Because trypanosomatids are one of the few organisms that do not synthesize the essential cofactor, heme, these parasites sequester the most common form, heme B, from their hosts. Once acquired, the parasites derivatize heme B to heme A by two sequential enzyme reactions. Although heme C is found in many cytochrome and proteins, heme A is the cofactor of only one known protein, cytochrome oxidase (CO). In a recent issue of the , Merli et al. [ (2017) 474, 2315-2332] demonstrate that the final step in the synthesis of heme A by heme A synthase (TcCox15) and the subsequent activity of CO are essential for infectivity and replication of .