Apicomplexan parasites contain a single lipoic acid synthase located in the plastid

• Published in: FEBS letters 2003-07, Vol.547 (1), p.80-86
• Main Authors: Thomsen-Zieger, Nadine, Schachtner, Joachim, Seeber, Frank
• Format: Article
• Language: English
• Subjects: ACP, acyl carrier protein; Amino Acid Sequence; Animals; Apicoplast; Base Sequence; BCDC, branched-chain 2-oxo acid dehydrogenase complex; Binding Sites; Cloning, Molecular; DNA Primers; EST, expressed sequence tag; GDC, glycine decarboxylase complex; GFP, green fluorescent protein; Iron–sulfur protein; LA, lipoic acid; LipA, lipoic acid synthase; Molecular Sequence Data; N-LipA/mycGFP, N-terminal TgLipA fused with myc-tagged GFP; OGDC, 2-oxoglutarate dehydrogenase complex; Organellar targeting; PDC, pyruvate dehydrogenase complex; Plasmodium falciparum; Plastids - enzymology; Plastids - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Sulfurtransferases - chemistry; Sulfurtransferases - genetics; Sulfurtransferases - metabolism; TgLipA, Toxoplasma gondii LipA; Toxoplasma - classification; Toxoplasma - enzymology; Toxoplasma gondii
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)00673-2

Apicomplexan parasites contain a vestigial plastid called apicoplast which has been suggested to be a site of [Fe–S] cluster biogenesis. Here we report the cloning of lipoic acid synthase (LipA) from Toxoplasma gondii, a well known [Fe–S] protein. It is able to complement a LipA-deficient Escherichia coli strain, clearly demonstrating that the parasite protein is a functional LipA. The N-terminus of T. gondii LipA is unusual with respect to an internal signal peptide preceding an apicoplast targeting domain. Nevertheless, it efficiently targets a reporter protein to the apicoplast of T. gondii whereas co-localization with the fluorescently labeled mitochondrion was not detected. In silico analysis of several apicomplexan genomes indicates that the parasites, in addition to the presumably apicoplast-resident pyruvate dehydrogenase complex, contain three other mitochondrion-localized target proteins for lipoic acid attachment. We also identified single genes for lipoyl (octanoyl)-acyl carrier protein:protein transferase (LipB) and lipoate protein ligase (LplA) in these genomes. It thus appears that unlike plants, which have only two LipA and LipB isoenzymes in both the chloroplasts and the mitochondria, Apicomplexa seem to use the second known lipoylating activity, LplA, for lipoylation in their mitochondrion.