Figure 1. A metabolic Catch-22 due to evolutionary acquired isoprenoid dependency.

Schematic representation of the putative evolution of the apicoplast and its metabolism. The ancestor of apicomplexans arose from the endosymbiotic merger of a protist host and a single celled red alga. The host likely benefited from the symbiont's ability to photosynthesize. Initially there were two redundant isoprenoid synthesis pathways: a cytoplasmic pathway (likely using the mevalonate pathway as ciliates still do [47]) and a plastid DOXP pathway. Note that both pathways have multiple enzymatic steps and are shown highly simplified here. The cytoplasmic pathway was lost producing dependency. This forced maintenance of the apicoplast even after loss of photosynthesis (lower panel). High concentrations of exogenously supplied IPP can overcome this dependency and thus rescue clindamycin induced loss of the organelle [31] (clindamycin specifically blocks apicoplast protein synthesis). Fos, fosmidomycin; N, nucleus; P, plastid; Statin, the active principle of the cholesterol-lowering drug Lipitor).