Apicomplexan parasites of the genus Eimeria are the major causative agent of avian coccidiosis, leading to high economic losses in the poultry industry. Recent results show that Eimeria tenella harbours an apicoplast organelle, and that a key biosynthetic enzyme, enoyl reductase, is located in this organelle. In related parasites, enoyl reductase is one component of a type II fatty acid synthase (FAS) and has proven to be an attractive target for antimicrobial compounds. We cloned and expressed the mature form of E. tenella enoyl reductase (EtENR) for biochemical and structural studies. Recombinant EtENR exhibits NADH-dependent enoyl reductase activity and is inhibited by triclosan with an IC50 value of 60 nm. The crystal structure of EtENR reveals overall similarity with other ENR enzymes; however, the active site of EtENR is unoccupied, a state rarely observed in other ENR structures. Furthermore, the position of the central beta-sheet appears to block NADH binding and would require significant movement to allow NADH binding, a feature not previously seen in the ENR family. We analysed the E. tenella genomic database for orthologues of well-characterized bacterial and apicomplexan FAS enzymes and identified 6 additional genes, suggesting that E. tenella contains a type II FAS capable of synthesizing saturated, but not unsaturated, fatty acids. Interestingly, we also identified sequences that appear to encode multifunctional type I FAS enzymes, a feature also observed in Toxoplasma gondii, highlighting the similarity between these apicomplexan parasites.

The parasitic protozoan Toxoplasma gondii and its relatives (e.g. Plasmodium spp., which cause malaria) constitute a major global health problem. In recent years, the elucidation of biological processes in these parasites has accelerated with the application of genetic and genomic methodologies. Genetic analyses in T. gondii have revealed a remarkably stable 87 Mb (megabase) nuclear genome consisting of 11 chromosomes showing little variation across strains. Population studies demonstrate that the small amount of variation defines three clonal lineages where phenotypes such as virulence are associated with a single lineage. The random generation of cDNA (complementary DNA) sequences derived from different strains and developmental stages has highlighted the genetic differences underlying observed phenotypic variation. T. gondii also contains an extrachromosomal 35 kb (kilobase) circular DNA within an organelle with plastid-like properties. The limited coding capacity of the 35 kb organellar genome suggests that proteins responsible for organelle function(s) must be encoded by the nucleus. Scrutiny of T. gondii nuclear cDNA sequences has uncovered a number of proteins thought to carry out essential roles in the organelle (e.g. fatty acid biosynthesis). The synergism between these seemingly unrelated genomic studies has provided a greater understanding of parasite pathogenesis and has identified several new targets for chemotherapy.