Library of Apicomplexan Metabolic Pathways: a manually curated database for metabolic pathways of apicomplexan parasites

Abstract

The Library of Apicomplexan Metabolic Pathways (LAMP, http://www.llamp.net) is a web database that provides near complete mapping from genes to the central metabolic functions for some of the prominent intracellular parasites of the phylum Apicomplexa. This phylum includes the causative agents of malaria, toxoplasmosis and theileriosis—diseases with a huge economic and social impact. A number of apicomplexan genomes have been sequenced, but the accurate annotation of gene function remains challenging. We have adopted an approach called metabolic reconstruction, in which genes are systematically assigned to functions within pathways/networks for Toxoplasma gondii, Neospora caninum, Cryptosporidium and Theileria species, and Babesia bovis. Several functions missing from pathways have been identified, where the corresponding gene for an essential process appears to be absent from the current genome annotation. For each species, LAMP contains interactive diagrams of each pathway, hyperlinked to external resources and annotated with detailed information, including the sources of evidence used. We have also developed a section to highlight the overall metabolic capabilities of each species, such as the ability to synthesize or the dependence on the host for a particular metabolite. We expect this new database will become a valuable resource for fundamental and applied research on the Apicomplexa.

Evolution of mitosome metabolism and invasion-related proteins in Cryptosporidium

“…The oxoglutarate dehydrogenase complex (OGDH) from the TCA cycle can become active when it couples with two cofactors, thiamine pyrophosphate (TPP) and lipoic acid. Among apicomplexans, only P. falciparum has the ability to synthesize thiamine de novo [21]. C. andersoni has to salvage TPP directly from the host, although its transporter has not been identified.…”

“…Both IPP and DMAPP are transported into the mitochondrion and condensed into farnesyl diphosphate (FPP) and polyprenyl diphosphate (PPP) [21, 23]. All Cryptosporidium spp.…”

“…Within the oxidative phosphorylation pathway on the inner mitochondrial membrane, the classical NADH dehydrogenase multi-protein complex, named complex I, is substituted by an alternative single NADH dehydrogenase in most apicomplexan parasites [21]. Similar to P. falciparum and T. gondii , which use three other multi-protein complexes (II-IV) to transfer electrons to oxygen, C. andersoni has the complete complex II, succinate dehydrogenase, which is also involved in the TCA cycle, and one subunit of complex III, ubiquinol-cytochrome c oxidoreductase.…”

Pantothenic Acid Biosynthesis in the Parasite Toxoplasma gondii: a Target for Chemotherapy

“…These genes are annotated in ToxoDB/EuPathDB (accession numbers TGME49_257050 and TGME49_265870), with patterns of detectable protein expression in tachyzoites and constitutive gene expression throughout the life cycle (i.e., bradyzoites, tachyzoites, and oocysts). The enzyme-encoding genes are also detectable in Neospora caninum (36).…”

“…All steps for synthesis except for the terminal step with dephospho-CoA kinase were identified in metabolic reconstructions (in EuPathDB and the Library of Apcomplexan Metabolic Pathways), and our software detected orthologs with high levels of similarity (E values of 2.9eϪ49 for T. gondii and 1.6eϪ51 for N. caninum) that are found in the genome sequences (36). Interestingly, the related apicomplexan parasite Plasmodium falciparum, the etiological agent of malaria, encodes the enzymes for the metabolism of pantothenate to coenzyme A, but genes encoding pantothenate biosynthetic enzymes have not been found and were not detectable in our analysis using SHARKhunt (30).…”