{"gene":"TG_263785","gene_symbol":"CDS2","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2017,"finding":"TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase that localizes to the apicoplast of T. gondii, distinct from the eukaryotic-type TgCDS1 which resides in the endoplasmic reticulum.","method":"Subcellular fractionation/localization experiments distinguishing two CDS isoforms by compartmental distribution","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional context, single lab, multiple orthogonal methods (genetics, lipidomics, localization)","pmids":["28314772"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"Deletion of TgCDS2 specifically reduces phosphatidylglycerol levels in T. gondii, indicating that the apicoplast-localized CDP-DAG pool produced by TgCDS2 is used preferentially for phosphatidylglycerol synthesis in the mitochondria.","method":"Conditional gene deletion combined with lipidomic analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic knockout with specific lipidomic phenotype readout, single lab, two orthogonal methods (genetics + lipidomics)","pmids":["28314772"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"TgCDS2 cooperates with TgCDS1 for lipid biogenesis: the residual growth of a TgCDS1 conditional knockdown mutant was completely abolished by consecutive deletion of TgCDS2, demonstrating that the two enzymes together are essential for parasite survival.","method":"Genetic epistasis via consecutive conditional knockdown of TgCDS1 and deletion of TgCDS2; parasite growth assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis by double-mutant analysis, single lab, defined growth phenotype","pmids":["28314772"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase localized to the apicoplast of T. gondii that produces a CDP-DAG pool used specifically for phosphatidylglycerol synthesis in the mitochondria, and cooperates with the ER-resident TgCDS1 to sustain essential phospholipid biogenesis required for parasite replication."},"narrative":{"mechanistic_narrative":"TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase that localizes to the apicoplast of Toxoplasma gondii, functioning in parallel with the eukaryotic-type, ER-resident TgCDS1 to sustain phospholipid biogenesis [PMID:28314772]. The apicoplast-derived CDP-DAG pool it produces is channeled preferentially toward phosphatidylglycerol synthesis, as deletion of TgCDS2 specifically depletes phosphatidylglycerol [PMID:28314772]. The two isoforms are functionally cooperative and collectively essential: deleting TgCDS2 in a TgCDS1-knockdown background abolishes the residual parasite growth, establishing that combined CDP-DAG production supports parasite replication [PMID:28314772]. Beyond these compartmentalized activities and their genetic interaction, no further mechanistic detail on TgCDS2 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Establishing that T. gondii encodes two distinct CDP-diacylglycerol synthases resolved where CDP-DAG is generated in the parasite, revealing an apicoplast-localized prokaryotic-type enzyme separate from the ER-resident eukaryotic-type isoform.","evidence":"Subcellular fractionation and localization distinguishing TgCDS2 (apicoplast) from TgCDS1 (ER)","pmids":["28314772"],"confidence":"Medium","gaps":["Direct enzymatic characterization of TgCDS2 CDP-DAG synthase activity not shown","No structural model of the enzyme"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"Linking TgCDS2 to a specific lipid output answered what the apicoplast CDP-DAG pool is used for, showing it feeds phosphatidylglycerol synthesis in the mitochondria.","evidence":"Conditional gene deletion combined with lipidomic analysis showing specific reduction of phosphatidylglycerol","pmids":["28314772"],"confidence":"Medium","gaps":["Mechanism of CDP-DAG transfer from apicoplast to mitochondria not defined","Enzymes downstream converting CDP-DAG to phosphatidylglycerol not identified in this study"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"Genetic epistasis clarified whether the two CDS isoforms are redundant or cooperative, demonstrating they are jointly essential for parasite survival.","evidence":"Consecutive conditional knockdown of TgCDS1 with deletion of TgCDS2 and parasite growth assays","pmids":["28314772"],"confidence":"Medium","gaps":["Extent of functional overlap versus division of labor between the two enzymes not fully resolved","Whether TgCDS2 loss alone impairs replication under standard conditions not stated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical activity, structure, and regulation of TgCDS2, and the trafficking route coupling apicoplast CDP-DAG to mitochondrial phosphatidylglycerol synthesis, remain uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in vitro reconstitution of TgCDS2 enzymatic activity","No structural information","Interorganelle lipid transport mechanism unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGCDS1 (FUNCTIONALLY COOPERATIVE ER-RESIDENT CDS ISOFORM)"],"other_free_text":["Apicoplast-localized prokaryotic-type CDP-diacylglycerol synthase; produces a CDP-DAG pool preferentially channeled to mitochondrial phosphatidylglycerol synthesis.","Jointly essential with TgCDS1 for parasite replication."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"28314772","id":"PMC_28314772","title":"Two phylogenetically and compartmentally distinct CDP-diacylglycerol synthases cooperate for lipid biogenesis in Toxoplasma gondii.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28314772","citation_count":27,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3051,"output_tokens":798,"usd":0.010561,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5616,"output_tokens":1860,"usd":0.03729,"stage2_stop_reason":"end_turn"},"total_usd":0.047851,"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\": 2017,\n      \"finding\": \"TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase that localizes to the apicoplast of T. gondii, distinct from the eukaryotic-type TgCDS1 which resides in the endoplasmic reticulum.\",\n      \"method\": \"Subcellular fractionation/localization experiments distinguishing two CDS isoforms by compartmental distribution\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional context, single lab, multiple orthogonal methods (genetics, lipidomics, localization)\",\n      \"pmids\": [\"28314772\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Deletion of TgCDS2 specifically reduces phosphatidylglycerol levels in T. gondii, indicating that the apicoplast-localized CDP-DAG pool produced by TgCDS2 is used preferentially for phosphatidylglycerol synthesis in the mitochondria.\",\n      \"method\": \"Conditional gene deletion combined with lipidomic analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic knockout with specific lipidomic phenotype readout, single lab, two orthogonal methods (genetics + lipidomics)\",\n      \"pmids\": [\"28314772\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TgCDS2 cooperates with TgCDS1 for lipid biogenesis: the residual growth of a TgCDS1 conditional knockdown mutant was completely abolished by consecutive deletion of TgCDS2, demonstrating that the two enzymes together are essential for parasite survival.\",\n      \"method\": \"Genetic epistasis via consecutive conditional knockdown of TgCDS1 and deletion of TgCDS2; parasite growth assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis by double-mutant analysis, single lab, defined growth phenotype\",\n      \"pmids\": [\"28314772\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase localized to the apicoplast of T. gondii that produces a CDP-DAG pool used specifically for phosphatidylglycerol synthesis in the mitochondria, and cooperates with the ER-resident TgCDS1 to sustain essential phospholipid biogenesis required for parasite replication.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgCDS2 is a prokaryotic-type CDP-diacylglycerol synthase that localizes to the apicoplast of Toxoplasma gondii, functioning in parallel with the eukaryotic-type, ER-resident TgCDS1 to sustain phospholipid biogenesis [#0]. The apicoplast-derived CDP-DAG pool it produces is channeled preferentially toward phosphatidylglycerol synthesis, as deletion of TgCDS2 specifically depletes phosphatidylglycerol [#1]. The two isoforms are functionally cooperative and collectively essential: deleting TgCDS2 in a TgCDS1-knockdown background abolishes the residual parasite growth, establishing that combined CDP-DAG production supports parasite replication [#2]. Beyond these compartmentalized activities and their genetic interaction, no further mechanistic detail on TgCDS2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing that T. gondii encodes two distinct CDP-diacylglycerol synthases resolved where CDP-DAG is generated in the parasite, revealing an apicoplast-localized prokaryotic-type enzyme separate from the ER-resident eukaryotic-type isoform.\",\n      \"evidence\": \"Subcellular fractionation and localization distinguishing TgCDS2 (apicoplast) from TgCDS1 (ER)\",\n      \"pmids\": [\"28314772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct enzymatic characterization of TgCDS2 CDP-DAG synthase activity not shown\", \"No structural model of the enzyme\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Linking TgCDS2 to a specific lipid output answered what the apicoplast CDP-DAG pool is used for, showing it feeds phosphatidylglycerol synthesis in the mitochondria.\",\n      \"evidence\": \"Conditional gene deletion combined with lipidomic analysis showing specific reduction of phosphatidylglycerol\",\n      \"pmids\": [\"28314772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of CDP-DAG transfer from apicoplast to mitochondria not defined\", \"Enzymes downstream converting CDP-DAG to phosphatidylglycerol not identified in this study\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Genetic epistasis clarified whether the two CDS isoforms are redundant or cooperative, demonstrating they are jointly essential for parasite survival.\",\n      \"evidence\": \"Consecutive conditional knockdown of TgCDS1 with deletion of TgCDS2 and parasite growth assays\",\n      \"pmids\": [\"28314772\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Extent of functional overlap versus division of labor between the two enzymes not fully resolved\", \"Whether TgCDS2 loss alone impairs replication under standard conditions not stated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity, structure, and regulation of TgCDS2, and the trafficking route coupling apicoplast CDP-DAG to mitochondrial phosphatidylglycerol synthesis, remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro reconstitution of TgCDS2 enzymatic activity\", \"No structural information\", \"Interorganelle lipid transport mechanism unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004605\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006655\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0008654\", \"supporting_discovery_ids\": [1, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgCDS1 (functionally cooperative ER-resident CDS isoform)\"],\n    \"other_free_text\": [\n      \"Apicoplast-localized prokaryotic-type CDP-diacylglycerol synthase; produces a CDP-DAG pool preferentially channeled to mitochondrial phosphatidylglycerol synthesis.\",\n      \"Jointly essential with TgCDS1 for parasite replication.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_263785","name":"CDS2","product":"phosphatidate cytidylyltransferase CDS2","uniprot_acc":"S8F8C8","chromosome":"TGME49_chrVIIb","start_pos":323502},{"strain":"GT1","gene_id":"TGGT1_263785","name":null,"product":"phosphatidate cytidylyltransferase","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":297442},{"strain":"RH88","gene_id":"TGRH88_067220","name":null,"product":"phosphatidate cytidylyltransferase","uniprot_acc":null,"chromosome":"CM023089","start_pos":335667},{"strain":"VEG","gene_id":"TGVEG_263785","name":null,"product":"phosphatidate cytidylyltransferase","uniprot_acc":"V4ZHK2","chromosome":"TGVEG_chrVIIb","start_pos":328534}]}