{"gene":"TG_251550","gene_symbol":"","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2018,"finding":"TgACBP1 possesses acyl-CoA binding activity, confirmed by fluorimetric binding assay and yeast complementation, functioning as a cytosolic acyl-CoA transporter for long-chain acyl-CoA esters in Toxoplasma lipid metabolism.","method":"Fluorimetric binding assay and yeast complementation assay","journal":"Cellular Microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal biochemical methods (fluorimetric binding assay + yeast complementation) in a single study confirming acyl-CoA binding activity","pmids":["30362657"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Disruption of TgACBP1 alone causes no obvious growth phenotype, but double disruption of TgACBP1 and TgSCP2 results in defects in intracellular growth and reduced virulence in mice, demonstrating synergistic roles in lipid metabolism.","method":"Genetic disruption (single and double knockout), intracellular growth assay, mouse virulence assay","journal":"Cellular Microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined cellular and in vivo phenotypic readouts, single lab study","pmids":["30362657"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Disruption of TgACBP1 alone leads to decreased abundance of C18:1 fatty acid; double disruption of TgACBP1 and TgSCP2 further reduces C18:1, C22:1, and C24:1 abundance and decreases synthesis rates of C18:0, C22:1, and C24:1, indicating TgACBP1 contributes to fatty acid elongation/transport.","method":"Gas chromatography-mass spectrometry (GC-MS) and 13C-labelling assay combined with GC-MS","journal":"Cellular Microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal metabolic methods (GC-MS lipidomics + isotope labelling) in single lab study","pmids":["30362657"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Double disruption of TgACBP1 and TgSCP2 causes serious defects in production of glycerides and phospholipids, placing TgACBP1 in a pathway required for glycerophospholipid biosynthesis.","method":"HPLC coupled with high-resolution mass spectrometry (HPLC-HRMS) lipidomic analysis","journal":"Cellular Microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct lipidomic readout from genetic disruption, single lab, single method for this specific finding","pmids":["30362657"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgACBP1 is a cytosolic acyl-CoA binding protein that, together with TgSCP2, transports long-chain acyl-CoA esters to support fatty acid elongation and glycerophospholipid biosynthesis in Toxoplasma gondii; loss of both proteins synergistically impairs intracellular growth, virulence, and production of very long-chain fatty acids, glycerides, and phospholipids, while loss of TgACBP1 alone reduces C18:1 levels without an obvious growth phenotype."},"narrative":{"mechanistic_narrative":"TgACBP1 is a cytosolic acyl-CoA binding protein of Toxoplasma gondii that binds long-chain acyl-CoA esters and functions in fatty acid elongation and glycerophospholipid biosynthesis [PMID:30362657]. Its acyl-CoA binding activity is established by direct fluorimetric binding and by rescue in a yeast complementation assay [PMID:30362657]. Loss of TgACBP1 alone reduces C18:1 fatty acid abundance without an overt growth phenotype, but combined disruption of TgACBP1 and TgSCP2 synergistically impairs intracellular growth and murine virulence [PMID:30362657], further depletes long- and very-long-chain fatty acids (C18:1, C22:1, C24:1) and their synthesis rates [PMID:30362657], and causes severe defects in glyceride and phospholipid production [PMID:30362657], placing the two proteins in a shared, partially redundant lipid-transport pathway. Beyond this single study, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Whether TgACBP1 actually binds acyl-CoA and behaves as a functional acyl-CoA transporter was unknown; biochemical binding and cross-species rescue established it as a bona fide cytosolic acyl-CoA binding protein.","evidence":"Fluorimetric acyl-CoA binding assay and yeast complementation in Toxoplasma gondii","pmids":["30362657"],"confidence":"Medium","gaps":["No structural basis for acyl-CoA selectivity","Range of acyl-chain lengths bound not fully delineated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"It was unclear whether TgACBP1 is individually essential; genetic disruption showed it is dispensable alone but functionally redundant with TgSCP2, revealing synergistic control of growth and virulence.","evidence":"Single and double genetic knockouts with intracellular growth and mouse virulence assays in Toxoplasma gondii","pmids":["30362657"],"confidence":"Medium","gaps":["Molecular basis of TgACBP1/TgSCP2 redundancy not defined","Whether the two proteins physically interact or act sequentially unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"The metabolic consequence of losing TgACBP1 was unknown; lipidomic and isotope-tracing analyses linked it to fatty acid elongation, showing reduced C18:1 alone and broader long-/very-long-chain fatty acid defects when combined with TgSCP2 loss.","evidence":"GC-MS lipidomics with 13C-labelling in Toxoplasma gondii","pmids":["30362657"],"confidence":"Medium","gaps":["Direct coupling of acyl-CoA transport to specific elongase reactions not shown","Contribution to individual elongation steps not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"Whether the fatty acid defects propagate to membrane lipid synthesis was open; lipidomics showed double disruption severely impairs glyceride and phospholipid production, placing TgACBP1 upstream of glycerophospholipid biosynthesis.","evidence":"HPLC-HRMS lipidomic analysis of knockout parasites in Toxoplasma gondii","pmids":["30362657"],"confidence":"Medium","gaps":["Specific phospholipid species affected not fully catalogued","Whether defect is direct substrate-supply or indirect not distinguished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TgACBP1 physically and functionally coordinates with TgSCP2, its structural determinants of acyl-CoA binding, and its regulation within the parasite lipid network remain uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reported protein-protein interaction data for TgACBP1/TgSCP2","No structural model of TgACBP1","No evidence spanning multiple T. gondii strains"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGSCP2"],"other_free_text":["Functionally redundant with TgSCP2: single TgACBP1 disruption is phenotypically silent for growth, whereas TgACBP1/TgSCP2 double disruption impairs intracellular growth and murine virulence [#1].","TgACBP1 loss selectively reduces C18:1; combined loss with TgSCP2 further depletes C22:1 and C24:1 and lowers synthesis of C18:0, C22:1, and C24:1 [#2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"30362657","id":"PMC_30362657","title":"Synergistic roles of acyl-CoA binding protein (ACBP1) and sterol carrier protein 2 (SCP2) in Toxoplasma lipid metabolism.","date":"2018","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30362657","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3043,"output_tokens":1101,"usd":0.012822,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6007,"output_tokens":2157,"usd":0.04198,"stage2_stop_reason":"end_turn"},"total_usd":0.054802,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"TgACBP1 possesses acyl-CoA binding activity, confirmed by fluorimetric binding assay and yeast complementation, functioning as a cytosolic acyl-CoA transporter for long-chain acyl-CoA esters in Toxoplasma lipid metabolism.\",\n      \"method\": \"Fluorimetric binding assay and yeast complementation assay\",\n      \"journal\": \"Cellular Microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal biochemical methods (fluorimetric binding assay + yeast complementation) in a single study confirming acyl-CoA binding activity\",\n      \"pmids\": [\"30362657\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Disruption of TgACBP1 alone causes no obvious growth phenotype, but double disruption of TgACBP1 and TgSCP2 results in defects in intracellular growth and reduced virulence in mice, demonstrating synergistic roles in lipid metabolism.\",\n      \"method\": \"Genetic disruption (single and double knockout), intracellular growth assay, mouse virulence assay\",\n      \"journal\": \"Cellular Microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined cellular and in vivo phenotypic readouts, single lab study\",\n      \"pmids\": [\"30362657\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Disruption of TgACBP1 alone leads to decreased abundance of C18:1 fatty acid; double disruption of TgACBP1 and TgSCP2 further reduces C18:1, C22:1, and C24:1 abundance and decreases synthesis rates of C18:0, C22:1, and C24:1, indicating TgACBP1 contributes to fatty acid elongation/transport.\",\n      \"method\": \"Gas chromatography-mass spectrometry (GC-MS) and 13C-labelling assay combined with GC-MS\",\n      \"journal\": \"Cellular Microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal metabolic methods (GC-MS lipidomics + isotope labelling) in single lab study\",\n      \"pmids\": [\"30362657\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Double disruption of TgACBP1 and TgSCP2 causes serious defects in production of glycerides and phospholipids, placing TgACBP1 in a pathway required for glycerophospholipid biosynthesis.\",\n      \"method\": \"HPLC coupled with high-resolution mass spectrometry (HPLC-HRMS) lipidomic analysis\",\n      \"journal\": \"Cellular Microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct lipidomic readout from genetic disruption, single lab, single method for this specific finding\",\n      \"pmids\": [\"30362657\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgACBP1 is a cytosolic acyl-CoA binding protein that, together with TgSCP2, transports long-chain acyl-CoA esters to support fatty acid elongation and glycerophospholipid biosynthesis in Toxoplasma gondii; loss of both proteins synergistically impairs intracellular growth, virulence, and production of very long-chain fatty acids, glycerides, and phospholipids, while loss of TgACBP1 alone reduces C18:1 levels without an obvious growth phenotype.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgACBP1 is a cytosolic acyl-CoA binding protein of Toxoplasma gondii that binds long-chain acyl-CoA esters and functions in fatty acid elongation and glycerophospholipid biosynthesis [#0]. Its acyl-CoA binding activity is established by direct fluorimetric binding and by rescue in a yeast complementation assay [#0]. Loss of TgACBP1 alone reduces C18:1 fatty acid abundance without an overt growth phenotype, but combined disruption of TgACBP1 and TgSCP2 synergistically impairs intracellular growth and murine virulence [#1], further depletes long- and very-long-chain fatty acids (C18:1, C22:1, C24:1) and their synthesis rates [#2], and causes severe defects in glyceride and phospholipid production [#3], placing the two proteins in a shared, partially redundant lipid-transport pathway. Beyond this single study, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether TgACBP1 actually binds acyl-CoA and behaves as a functional acyl-CoA transporter was unknown; biochemical binding and cross-species rescue established it as a bona fide cytosolic acyl-CoA binding protein.\",\n      \"evidence\": \"Fluorimetric acyl-CoA binding assay and yeast complementation in Toxoplasma gondii\",\n      \"pmids\": [\"30362657\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural basis for acyl-CoA selectivity\", \"Range of acyl-chain lengths bound not fully delineated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"It was unclear whether TgACBP1 is individually essential; genetic disruption showed it is dispensable alone but functionally redundant with TgSCP2, revealing synergistic control of growth and virulence.\",\n      \"evidence\": \"Single and double genetic knockouts with intracellular growth and mouse virulence assays in Toxoplasma gondii\",\n      \"pmids\": [\"30362657\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of TgACBP1/TgSCP2 redundancy not defined\", \"Whether the two proteins physically interact or act sequentially unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The metabolic consequence of losing TgACBP1 was unknown; lipidomic and isotope-tracing analyses linked it to fatty acid elongation, showing reduced C18:1 alone and broader long-/very-long-chain fatty acid defects when combined with TgSCP2 loss.\",\n      \"evidence\": \"GC-MS lipidomics with 13C-labelling in Toxoplasma gondii\",\n      \"pmids\": [\"30362657\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct coupling of acyl-CoA transport to specific elongase reactions not shown\", \"Contribution to individual elongation steps not resolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether the fatty acid defects propagate to membrane lipid synthesis was open; lipidomics showed double disruption severely impairs glyceride and phospholipid production, placing TgACBP1 upstream of glycerophospholipid biosynthesis.\",\n      \"evidence\": \"HPLC-HRMS lipidomic analysis of knockout parasites in Toxoplasma gondii\",\n      \"pmids\": [\"30362657\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific phospholipid species affected not fully catalogued\", \"Whether defect is direct substrate-supply or indirect not distinguished\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgACBP1 physically and functionally coordinates with TgSCP2, its structural determinants of acyl-CoA binding, and its regulation within the parasite lipid network remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reported protein-protein interaction data for TgACBP1/TgSCP2\", \"No structural model of TgACBP1\", \"No evidence spanning multiple T. gondii strains\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0000062\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0034625\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006650\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgSCP2\"],\n    \"other_free_text\": [\n      \"Functionally redundant with TgSCP2: single TgACBP1 disruption is phenotypically silent for growth, whereas TgACBP1/TgSCP2 double disruption impairs intracellular growth and murine virulence [#1].\",\n      \"TgACBP1 loss selectively reduces C18:1; combined loss with TgSCP2 further depletes C22:1 and C24:1 and lowers synthesis of C18:0, C22:1, and C24:1 [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_251550","name":null,"product":"acyl-CoA binding protein ACBP1","uniprot_acc":"A0A125YSH4","chromosome":"TGME49_chrXII","start_pos":5453589},{"strain":"GT1","gene_id":"TGGT1_251550","name":null,"product":"acyl-coa-binding protein","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":5375924},{"strain":"RH88","gene_id":"TGRH88_064410","name":null,"product":"acyl-coa-binding protein","uniprot_acc":null,"chromosome":"CM023093","start_pos":5535303},{"strain":"VEG","gene_id":"TGVEG_251550","name":null,"product":"acyl-coa-binding protein","uniprot_acc":"B9PRJ2","chromosome":"TGVEG_chrXII","start_pos":5445215}]}