{"gene":"PF3D7_1344600","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2004,"finding":"LipA (lipoic acid synthase, PF3D7_1344600) localizes to the apicoplast of P. falciparum intraerythrocytic stages, as established by GFP fusion of its N-terminal sequence overexpressed in parasites. Its functionality was confirmed by complementation of E. coli lipA-deficient mutants.","method":"GFP fusion live imaging (subcellular localization) + bacterial complementation assay (functional validation)","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct localization by GFP fusion in P. falciparum combined with independent functional complementation in bacteria, two orthogonal methods in a single study","pmids":["15225307"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"LipA (PF3D7_1344600) is expressed at the protein level in P. falciparum intraerythrocytic stages, with maximal expression in early and late erythrocytic stages, as shown by Northern and Western blot analyses.","method":"Northern blot and Western blot","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — expression-level evidence by two blotting methods in a single study, not a direct mechanistic assay but establishes stage-specific protein presence","pmids":["15225307"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"LipA (PF3D7_1344600) together with LipB mediates de novo lipoic acid biosynthesis exclusively in the apicoplast of Plasmodium, where it generates lipoic acid from octanoyl-ACP supplied by the type II fatty acid synthesis pathway. This apicoplast-confined biosynthesis is the co-factor source for the acetyltransferase subunit of the apicoplast pyruvate dehydrogenase (PDH). LA biosynthesis was found not to be vital for intraerythrocytic development but is inferred to be required for liver stage development based on the phenotypic consequences of deleting FAS II and PDH components.","method":"Review synthesis of genetic deletion studies (FAS II/PDH component knockouts in Plasmodium); no direct LipA loss-of-function experiment described","journal":"Current pharmaceutical design","confidence":"Low","confidence_rationale":"Tier 4 / Weak — pathway placement is inferred from deletion of other components (FAS II, PDH), not from direct LipA/PF3D7_1344600 loss-of-function; single review paper","pmids":["22607141"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"LipA (PF3D7_1344600) is an apicoplast-localized lipoic acid synthase in P. falciparum that functions together with LipB to synthesize lipoic acid de novo from octanoyl-ACP (provided by FAS II), thereby supplying the essential cofactor to the acetyltransferase subunit of the apicoplast pyruvate dehydrogenase; its functionality has been confirmed by complementation of E. coli lipA mutants, and it is expressed maximally in early and late intraerythrocytic stages."},"narrative":{"mechanistic_narrative":"LipA (PF3D7_1344600) is an apicoplast-localized lipoic acid synthase of P. falciparum, established by GFP fusion imaging of its N-terminal targeting sequence in intraerythrocytic parasites and functionally validated by complementation of E. coli lipA-deficient mutants [PMID:15225307]. It is expressed at the protein level during intraerythrocytic development, with maximal abundance in early and late erythrocytic stages [PMID:15225307]. Within the apicoplast, LipA acts together with LipB in de novo lipoic acid biosynthesis, generating lipoic acid from octanoyl-ACP supplied by the type II fatty acid synthesis (FAS II) pathway to furnish the cofactor for the acetyltransferase subunit of the apicoplast pyruvate dehydrogenase [PMID:22607141]. Beyond this pathway placement and localization, no direct loss-of-function characterization of LipA (PF3D7_1344600) itself has been performed in the available corpus; its role in the apicoplast pathway is inferred from deletion of other FAS II and PDH components rather than from direct LipA knockout [PMID:22607141].","teleology":[{"year":2004,"claim":"It was unknown where in the parasite lipoic acid synthase acts and whether the predicted P. falciparum enzyme is a genuine lipoyl synthase; GFP targeting placed LipA in the apicoplast and bacterial complementation confirmed it is a functional lipoic acid synthase.","evidence":"GFP fusion of the N-terminal sequence for live-cell localization in P. falciparum plus complementation of an E. coli lipA-deficient mutant","pmids":["15225307"],"confidence":"High","gaps":["N-terminal GFP fusion establishes targeting but not the localization or activity of full-length endogenous LipA","Complementation shows enzymatic function in a heterologous host, not in situ activity or substrate specificity in the apicoplast","No direct enzymatic assay of the P. falciparum protein on its native substrate"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Whether and when LipA protein is present during blood-stage development was unresolved; blotting showed stage-specific protein expression peaking in early and late intraerythrocytic stages.","evidence":"Northern and Western blot analyses across intraerythrocytic stages in P. falciparum","pmids":["15225307"],"confidence":"Medium","gaps":["Expression timing does not establish functional requirement at any stage","No quantitation linking protein abundance to lipoic acid output"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"The metabolic context of LipA was unclear; synthesis of prior deletion studies placed LipA/LipB-mediated de novo lipoic acid biosynthesis exclusively in the apicoplast, drawing octanoyl-ACP from FAS II to supply the apicoplast PDH acetyltransferase.","evidence":"Review synthesis of FAS II and PDH component knockout phenotypes in Plasmodium; no direct LipA loss-of-function experiment","pmids":["22607141"],"confidence":"Low","gaps":["Pathway placement is inferred from deletion of other components, not from direct LipA/PF3D7_1344600 knockout","Blood-stage dispensability and inferred liver-stage requirement are not tested by targeting LipA itself","Physical interaction between LipA and LipB is not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Direct genetic and biochemical characterization of LipA (PF3D7_1344600) itself is still needed to define its native enzymatic activity, its physical partnership with LipB, and its stage-specific requirement.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct LipA loss-of-function phenotype in Plasmodium","No reconstituted enzymatic assay on octanoyl-ACP with the P. falciparum protein","No demonstrated LipA-LipB complex or structural data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["LIPB"],"other_free_text":["Functionally validated by complementation of E. coli lipA-deficient mutants [#0]","Protein expressed maximally in early and late intraerythrocytic stages [#1]","Supplies lipoic acid cofactor to the apicoplast pyruvate dehydrogenase acetyltransferase subunit; uses octanoyl-ACP from FAS II [#2]","Apicoplast lipoic acid biosynthesis inferred dispensable for intraerythrocytic development but required for liver-stage development based on FAS II/PDH deletions, not direct LipA knockout [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15225307","id":"PMC_15225307","title":"The human malaria parasite Plasmodium falciparum has distinct organelle-specific lipoylation pathways.","date":"2004","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/15225307","citation_count":64,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["LipA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22128915","id":"PMC_22128915","title":"Mitochondrial lipoic acid scavenging is essential for Plasmodium berghei liver stage development.","date":"2012","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22128915","citation_count":38,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22607141","id":"PMC_22607141","title":"Lipoic acid metabolism of Plasmodium--a suitable drug target.","date":"2012","source":"Current pharmaceutical design","url":"https://pubmed.ncbi.nlm.nih.gov/22607141","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["LipA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28655332","id":"PMC_28655332","title":"Conditional knock-out of lipoic acid protein ligase 1 reveals redundancy pathway for lipoic acid metabolism in Plasmodium berghei malaria parasite.","date":"2017","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/28655332","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["LipA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5012,"output_tokens":970,"usd":0.014793,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5695,"output_tokens":2015,"usd":0.039425,"stage2_stop_reason":"end_turn"},"total_usd":0.054218,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"LipA (lipoic acid synthase, PF3D7_1344600) localizes to the apicoplast of P. falciparum intraerythrocytic stages, as established by GFP fusion of its N-terminal sequence overexpressed in parasites. Its functionality was confirmed by complementation of E. coli lipA-deficient mutants.\",\n      \"method\": \"GFP fusion live imaging (subcellular localization) + bacterial complementation assay (functional validation)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by GFP fusion in P. falciparum combined with independent functional complementation in bacteria, two orthogonal methods in a single study\",\n      \"pmids\": [\"15225307\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"LipA (PF3D7_1344600) is expressed at the protein level in P. falciparum intraerythrocytic stages, with maximal expression in early and late erythrocytic stages, as shown by Northern and Western blot analyses.\",\n      \"method\": \"Northern blot and Western blot\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — expression-level evidence by two blotting methods in a single study, not a direct mechanistic assay but establishes stage-specific protein presence\",\n      \"pmids\": [\"15225307\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"LipA (PF3D7_1344600) together with LipB mediates de novo lipoic acid biosynthesis exclusively in the apicoplast of Plasmodium, where it generates lipoic acid from octanoyl-ACP supplied by the type II fatty acid synthesis pathway. This apicoplast-confined biosynthesis is the co-factor source for the acetyltransferase subunit of the apicoplast pyruvate dehydrogenase (PDH). LA biosynthesis was found not to be vital for intraerythrocytic development but is inferred to be required for liver stage development based on the phenotypic consequences of deleting FAS II and PDH components.\",\n      \"method\": \"Review synthesis of genetic deletion studies (FAS II/PDH component knockouts in Plasmodium); no direct LipA loss-of-function experiment described\",\n      \"journal\": \"Current pharmaceutical design\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — pathway placement is inferred from deletion of other components (FAS II, PDH), not from direct LipA/PF3D7_1344600 loss-of-function; single review paper\",\n      \"pmids\": [\"22607141\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"LipA (PF3D7_1344600) is an apicoplast-localized lipoic acid synthase in P. falciparum that functions together with LipB to synthesize lipoic acid de novo from octanoyl-ACP (provided by FAS II), thereby supplying the essential cofactor to the acetyltransferase subunit of the apicoplast pyruvate dehydrogenase; its functionality has been confirmed by complementation of E. coli lipA mutants, and it is expressed maximally in early and late intraerythrocytic stages.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"LipA (PF3D7_1344600) is an apicoplast-localized lipoic acid synthase of P. falciparum, established by GFP fusion imaging of its N-terminal targeting sequence in intraerythrocytic parasites and functionally validated by complementation of E. coli lipA-deficient mutants [#0]. It is expressed at the protein level during intraerythrocytic development, with maximal abundance in early and late erythrocytic stages [#1]. Within the apicoplast, LipA acts together with LipB in de novo lipoic acid biosynthesis, generating lipoic acid from octanoyl-ACP supplied by the type II fatty acid synthesis (FAS II) pathway to furnish the cofactor for the acetyltransferase subunit of the apicoplast pyruvate dehydrogenase [#2]. Beyond this pathway placement and localization, no direct loss-of-function characterization of LipA (PF3D7_1344600) itself has been performed in the available corpus; its role in the apicoplast pathway is inferred from deletion of other FAS II and PDH components rather than from direct LipA knockout [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"It was unknown where in the parasite lipoic acid synthase acts and whether the predicted P. falciparum enzyme is a genuine lipoyl synthase; GFP targeting placed LipA in the apicoplast and bacterial complementation confirmed it is a functional lipoic acid synthase.\",\n      \"evidence\": \"GFP fusion of the N-terminal sequence for live-cell localization in P. falciparum plus complementation of an E. coli lipA-deficient mutant\",\n      \"pmids\": [\"15225307\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"N-terminal GFP fusion establishes targeting but not the localization or activity of full-length endogenous LipA\",\n        \"Complementation shows enzymatic function in a heterologous host, not in situ activity or substrate specificity in the apicoplast\",\n        \"No direct enzymatic assay of the P. falciparum protein on its native substrate\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Whether and when LipA protein is present during blood-stage development was unresolved; blotting showed stage-specific protein expression peaking in early and late intraerythrocytic stages.\",\n      \"evidence\": \"Northern and Western blot analyses across intraerythrocytic stages in P. falciparum\",\n      \"pmids\": [\"15225307\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Expression timing does not establish functional requirement at any stage\",\n        \"No quantitation linking protein abundance to lipoic acid output\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The metabolic context of LipA was unclear; synthesis of prior deletion studies placed LipA/LipB-mediated de novo lipoic acid biosynthesis exclusively in the apicoplast, drawing octanoyl-ACP from FAS II to supply the apicoplast PDH acetyltransferase.\",\n      \"evidence\": \"Review synthesis of FAS II and PDH component knockout phenotypes in Plasmodium; no direct LipA loss-of-function experiment\",\n      \"pmids\": [\"22607141\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Pathway placement is inferred from deletion of other components, not from direct LipA/PF3D7_1344600 knockout\",\n        \"Blood-stage dispensability and inferred liver-stage requirement are not tested by targeting LipA itself\",\n        \"Physical interaction between LipA and LipB is not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Direct genetic and biochemical characterization of LipA (PF3D7_1344600) itself is still needed to define its native enzymatic activity, its physical partnership with LipB, and its stage-specific requirement.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct LipA loss-of-function phenotype in Plasmodium\",\n        \"No reconstituted enzymatic assay on octanoyl-ACP with the P. falciparum protein\",\n        \"No demonstrated LipA-LipB complex or structural data\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016992\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0009107\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"LipB\"],\n    \"other_free_text\": [\n      \"Functionally validated by complementation of E. coli lipA-deficient mutants [#0]\",\n      \"Protein expressed maximally in early and late intraerythrocytic stages [#1]\",\n      \"Supplies lipoic acid cofactor to the apicoplast pyruvate dehydrogenase acetyltransferase subunit; uses octanoyl-ACP from FAS II [#2]\",\n      \"Apicoplast lipoic acid biosynthesis inferred dispensable for intraerythrocytic development but required for liver-stage development based on FAS II/PDH deletions, not direct LipA knockout [#2]\"\n    ]\n  }\n}\n```","audit_flag":{"gene":"PF3D7_1344600","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0923600, PF3D7_1314600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1344600","name":null,"product":"lipoyl synthase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1357500","name":null,"product":"lipoyl synthase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1256700","name":null,"product":"lipoyl synthase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"LipA","evaluation":null}