{"gene":"TG_290970","gene_symbol":"SPT2","run_date":"2026-09-08T14:08:30","timeline":{"discoveries":[{"year":2022,"finding":"TgSPT2 is one of two serine palmitoyltransferases (with TgSPT1) in Toxoplasma gondii that function as part of the de novo ceramide synthesis pathway; deletion of TgSPT2 results in a perturbed sphingolipidome characterized by a drastic reduction in ceramides and ceramide phosphoethanolamines but not sphingomyelins.","method":"Gene deletion (knockout) combined with lipidomic analysis; phenotypic characterization in vitro and in vivo","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean gene knockout with lipidomic readout and in vivo phenotyping, single lab, multiple orthogonal methods (genetics + mass spectrometry-based lipidomics)","pmids":["35977499"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgSPT2 is a serine palmitoyltransferase in Toxoplasma gondii that functions in the de novo ceramide biosynthesis pathway, and its deletion leads to reduced ceramide and ceramide phosphoethanolamine levels, though the most pronounced fitness defects (invasion and chronic cyst formation) are primarily attributed to TgSPT1 loss."},"narrative":{"mechanistic_narrative":"TgSPT2 is one of two serine palmitoyltransferases in Toxoplasma gondii that operate within the de novo ceramide biosynthesis pathway [PMID:35977499]. Deletion of TgSPT2 perturbs the parasite sphingolipidome, producing a drastic reduction in ceramides and ceramide phosphoethanolamines while leaving sphingomyelins largely unaffected [PMID:35977499]. Beyond this genetic and lipidomic characterization [PMID:35977499], no further mechanistic detail on TgSPT2 has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"It was unknown which enzymes drive de novo ceramide synthesis in Toxoplasma; deletion of TgSPT2 established it as one of two serine palmitoyltransferases whose loss selectively collapses ceramide and ceramide phosphoethanolamine pools without affecting sphingomyelin.","evidence":"Gene knockout combined with mass spectrometry-based lipidomics and in vitro/in vivo phenotyping in T. gondii","pmids":["35977499"],"confidence":"Medium","gaps":["The individual biochemical activity of TgSPT2 versus TgSPT1 was not resolved; fitness defects were primarily attributed to TgSPT1.","No structural model, substrate specificity, or reconstituted enzymatic assay for TgSPT2.","Subcellular localization and regulation of TgSPT2 not established."],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TgSPT2 and TgSPT1 divide catalytic labor and whether TgSPT2 has a distinct substrate preference or regulatory role remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in vitro enzymatic characterization distinguishing TgSPT2 from TgSPT1.","No interaction or complex data for TgSPT2.","No localization data for TgSPT2."],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGSPT1"],"other_free_text":["Deletion of TgSPT2 reduces ceramides and ceramide phosphoethanolamines but not sphingomyelins [#0].","The most pronounced fitness defects (invasion, chronic cyst formation) are primarily attributed to TgSPT1 loss rather than TgSPT2 [#0]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35977499","id":"PMC_35977499","title":"Ceramide biosynthesis is critical for establishment of the intracellular niche of Toxoplasma gondii.","date":"2022","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/35977499","citation_count":19,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2842,"output_tokens":388,"usd":0.007173,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4998,"output_tokens":1159,"usd":0.026982,"stage2_stop_reason":"end_turn"},"total_usd":0.034155,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"TgSPT2 is one of two serine palmitoyltransferases (with TgSPT1) in Toxoplasma gondii that function as part of the de novo ceramide synthesis pathway; deletion of TgSPT2 results in a perturbed sphingolipidome characterized by a drastic reduction in ceramides and ceramide phosphoethanolamines but not sphingomyelins.\",\n      \"method\": \"Gene deletion (knockout) combined with lipidomic analysis; phenotypic characterization in vitro and in vivo\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean gene knockout with lipidomic readout and in vivo phenotyping, single lab, multiple orthogonal methods (genetics + mass spectrometry-based lipidomics)\",\n      \"pmids\": [\"35977499\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgSPT2 is a serine palmitoyltransferase in Toxoplasma gondii that functions in the de novo ceramide biosynthesis pathway, and its deletion leads to reduced ceramide and ceramide phosphoethanolamine levels, though the most pronounced fitness defects (invasion and chronic cyst formation) are primarily attributed to TgSPT1 loss.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgSPT2 is one of two serine palmitoyltransferases in Toxoplasma gondii that operate within the de novo ceramide biosynthesis pathway [#0]. Deletion of TgSPT2 perturbs the parasite sphingolipidome, producing a drastic reduction in ceramides and ceramide phosphoethanolamines while leaving sphingomyelins largely unaffected [#0]. Beyond this genetic and lipidomic characterization [#0], no further mechanistic detail on TgSPT2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"It was unknown which enzymes drive de novo ceramide synthesis in Toxoplasma; deletion of TgSPT2 established it as one of two serine palmitoyltransferases whose loss selectively collapses ceramide and ceramide phosphoethanolamine pools without affecting sphingomyelin.\",\n      \"evidence\": \"Gene knockout combined with mass spectrometry-based lipidomics and in vitro/in vivo phenotyping in T. gondii\",\n      \"pmids\": [\"35977499\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The individual biochemical activity of TgSPT2 versus TgSPT1 was not resolved; fitness defects were primarily attributed to TgSPT1.\",\n        \"No structural model, substrate specificity, or reconstituted enzymatic assay for TgSPT2.\",\n        \"Subcellular localization and regulation of TgSPT2 not established.\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgSPT2 and TgSPT1 divide catalytic labor and whether TgSPT2 has a distinct substrate preference or regulatory role remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro enzymatic characterization distinguishing TgSPT2 from TgSPT1.\",\n        \"No interaction or complex data for TgSPT2.\",\n        \"No localization data for TgSPT2.\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004758\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046513\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgSPT1\"],\n    \"other_free_text\": [\n      \"Deletion of TgSPT2 reduces ceramides and ceramide phosphoethanolamines but not sphingomyelins [#0].\",\n      \"The most pronounced fitness defects (invasion, chronic cyst formation) are primarily attributed to TgSPT1 loss rather than TgSPT2 [#0].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_290970","name":"SPT2","product":"serine palmitoyltransferase SPT2","uniprot_acc":"A0A125YGM8","chromosome":"TGME49_chrIX","start_pos":4002393},{"strain":"GT1","gene_id":"TGGT1_290970","name":null,"product":"8-amino-7-oxononanoate synthase","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":3811046},{"strain":"RH88","gene_id":"TGRH88_015320","name":null,"product":"8-amino-7-oxononanoate synthase","uniprot_acc":null,"chromosome":"CM023090","start_pos":4067079},{"strain":"VEG","gene_id":"TGVEG_290970","name":null,"product":"8-amino-7-oxononanoate synthase","uniprot_acc":"B9QEB0","chromosome":"TGVEG_chrIX","start_pos":4037801}]}