{"gene":"PF3D7_0826400","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2020,"finding":"An active cis-prenyltransferase (PF3D7_0826400/PfCPT) was confirmed in Plasmodium falciparum, catalyzing de novo biosynthesis of polyprenol chains (15–19 isoprene units) as part of the dolichol biosynthesis pathway; dolichol is subsequently generated via reduction of polyprenol by an active polyprenol reductase (PfPPRD).","method":"Metabolomics profiling combined with confirmation of enzymatic activity in P. falciparum intraerythrocytic and gametocyte stages","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — metabolomics plus confirmed enzymatic activity in parasite, single lab, no in vitro reconstitution or mutagenesis of the purified protein","pmids":["32764679"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PF3D7_0826400 (PfCPT)-dependent cis-polyisoprenoid biosynthesis produces a distinctive polyprenol and dolichol profile that changes throughout the intraerythrocytic asexual cycle and differs between asexual and gametocyte stages, indicating stage-specific regulation of CPT activity.","method":"Metabolomics profiling across parasite developmental stages","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single metabolomics method, no direct mechanistic dissection of CPT regulation","pmids":["32764679"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Phylogenetic analysis predicts that PF3D7_0826400 (PfCPT) is a catalytic subunit (CPT-CS) that requires a CPT accessory subunit (CPT-AS) to form an active heteromeric enzyme, analogous to other eukaryotic heteromeric cis-prenyltransferases; however, no CPT-AS partner has been experimentally identified in Plasmodium.","method":"Phylogenetic analysis (comparative/computational); no direct Plasmodium experiment performed","journal":"The FEBS journal","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/phylogenetic prediction only; no experimental validation in Plasmodium reported in this abstract","pmids":["40847593"],"is_preprint":false,"attribution":[]}],"current_model":"PF3D7_0826400 (PfCPT) is an active cis-prenyltransferase in Plasmodium falciparum that catalyzes de novo polyprenyl chain elongation (producing polyprenols of 15–19 isoprene units), with its activity varying across parasite developmental stages; the polyprenol product is subsequently reduced to dolichol by PfPPRD, and phylogenetic evidence suggests PfCPT functions as a catalytic subunit requiring an as-yet-unidentified accessory subunit to form a fully active heteromeric complex."},"narrative":{"mechanistic_narrative":"PF3D7_0826400 (CPT) is an active cis-prenyltransferase of Plasmodium falciparum that catalyzes de novo polyprenyl chain elongation, producing polyprenols of 15–19 isoprene units as the committed step of the parasite's dolichol biosynthesis pathway; the polyprenol product is subsequently reduced to dolichol by the polyprenol reductase PfPPRD [PMID:32764679]. Its cis-polyisoprenoid output yields a polyprenol and dolichol profile that varies across the intraerythrocytic asexual cycle and differs between asexual and gametocyte stages, indicating stage-specific regulation of the enzyme [PMID:32764679]. Phylogenetic analysis predicts CPT is the catalytic subunit of a heteromeric enzyme that would require an as-yet-unidentified accessory subunit, but no such partner has been experimentally identified in Plasmodium [PMID:40847593]. Beyond these findings, the enzyme has not been reconstituted in vitro, mutagenized, or structurally characterized in the available corpus.","teleology":[{"year":2020,"claim":"Whether Plasmodium falciparum encodes a functional cis-prenyltransferase feeding dolichol biosynthesis was resolved by confirming CPT catalyzes polyprenol chain elongation in the parasite.","evidence":"Metabolomics profiling plus confirmation of enzymatic activity in intraerythrocytic and gametocyte stages","pmids":["32764679"],"confidence":"Medium","gaps":["No in vitro reconstitution or mutagenesis of the purified protein","Chain-length specificity determinants not dissected","Subcellular localization of the enzyme not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To ask whether CPT output is developmentally controlled, polyprenol/dolichol profiles were tracked across stages, revealing stage-specific differences that imply regulated CPT activity.","evidence":"Metabolomics profiling across intraerythrocytic asexual and gametocyte developmental stages","pmids":["32764679"],"confidence":"Low","gaps":["Single lab, single metabolomics method with no direct mechanistic dissection of CPT regulation","Transcriptional versus post-translational control of activity unresolved","Whether profile changes reflect CPT abundance or activity is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"To address the enzyme's quaternary organization, phylogenetic analysis predicted CPT is a catalytic subunit requiring an accessory subunit for a fully active heteromeric complex.","evidence":"Comparative/phylogenetic analysis; no direct Plasmodium experiment performed","pmids":["40847593"],"confidence":"Low","gaps":["Computational prediction only, with no experimental validation in Plasmodium","No CPT accessory subunit partner identified in Plasmodium","Complex stoichiometry and requirement for activity untested"],"attribution":[]},{"year":null,"claim":"Whether CPT functions as a heteromeric enzyme in Plasmodium and the identity of any accessory subunit remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimentally identified CPT accessory subunit","No structural or reconstitution data for the putative complex"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPPRD (POLYPRENOL REDUCTASE; ACTS DOWNSTREAM ON CPT PRODUCT) [#0]"],"other_free_text":["Produces polyprenols of 15–19 isoprene units as the committed step of dolichol biosynthesis [#0]","Polyprenol/dolichol profile varies across intraerythrocytic asexual cycle and between asexual and gametocyte stages [#1]","Predicted catalytic subunit of a heteromeric cis-prenyltransferase requiring an unidentified accessory subunit [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32764679","id":"PMC_32764679","title":"Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32764679","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cis-prenyltransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38202761","id":"PMC_38202761","title":"Aptamer-Based Imaging of Polyisoprenoids in the Malaria Parasite.","date":"2023","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/38202761","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cis-prenyltransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40847593","id":"","title":"Evolutionary divergence and functional insights into the heteromeric cis-prenyltransferase of Paramecium tetraurelia.","date":"2025","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/40847593","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CPT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5208,"output_tokens":911,"usd":0.014644,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5621,"output_tokens":1679,"usd":0.03504,"stage2_stop_reason":"end_turn"},"total_usd":0.049684,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"An active cis-prenyltransferase (PF3D7_0826400/PfCPT) was confirmed in Plasmodium falciparum, catalyzing de novo biosynthesis of polyprenol chains (15–19 isoprene units) as part of the dolichol biosynthesis pathway; dolichol is subsequently generated via reduction of polyprenol by an active polyprenol reductase (PfPPRD).\",\n      \"method\": \"Metabolomics profiling combined with confirmation of enzymatic activity in P. falciparum intraerythrocytic and gametocyte stages\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — metabolomics plus confirmed enzymatic activity in parasite, single lab, no in vitro reconstitution or mutagenesis of the purified protein\",\n      \"pmids\": [\"32764679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_0826400 (PfCPT)-dependent cis-polyisoprenoid biosynthesis produces a distinctive polyprenol and dolichol profile that changes throughout the intraerythrocytic asexual cycle and differs between asexual and gametocyte stages, indicating stage-specific regulation of CPT activity.\",\n      \"method\": \"Metabolomics profiling across parasite developmental stages\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single metabolomics method, no direct mechanistic dissection of CPT regulation\",\n      \"pmids\": [\"32764679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Phylogenetic analysis predicts that PF3D7_0826400 (PfCPT) is a catalytic subunit (CPT-CS) that requires a CPT accessory subunit (CPT-AS) to form an active heteromeric enzyme, analogous to other eukaryotic heteromeric cis-prenyltransferases; however, no CPT-AS partner has been experimentally identified in Plasmodium.\",\n      \"method\": \"Phylogenetic analysis (comparative/computational); no direct Plasmodium experiment performed\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/phylogenetic prediction only; no experimental validation in Plasmodium reported in this abstract\",\n      \"pmids\": [\"40847593\"],\n      \"is_preprint\": false,\n      \"attribution\": []\n    }\n  ],\n  \"current_model\": \"PF3D7_0826400 (PfCPT) is an active cis-prenyltransferase in Plasmodium falciparum that catalyzes de novo polyprenyl chain elongation (producing polyprenols of 15–19 isoprene units), with its activity varying across parasite developmental stages; the polyprenol product is subsequently reduced to dolichol by PfPPRD, and phylogenetic evidence suggests PfCPT functions as a catalytic subunit requiring an as-yet-unidentified accessory subunit to form a fully active heteromeric complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0826400 (CPT) is an active cis-prenyltransferase of Plasmodium falciparum that catalyzes de novo polyprenyl chain elongation, producing polyprenols of 15\\u201319 isoprene units as the committed step of the parasite's dolichol biosynthesis pathway; the polyprenol product is subsequently reduced to dolichol by the polyprenol reductase PfPPRD [#0]. Its cis-polyisoprenoid output yields a polyprenol and dolichol profile that varies across the intraerythrocytic asexual cycle and differs between asexual and gametocyte stages, indicating stage-specific regulation of the enzyme [#1]. Phylogenetic analysis predicts CPT is the catalytic subunit of a heteromeric enzyme that would require an as-yet-unidentified accessory subunit, but no such partner has been experimentally identified in Plasmodium [#2]. Beyond these findings, the enzyme has not been reconstituted in vitro, mutagenized, or structurally characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether Plasmodium falciparum encodes a functional cis-prenyltransferase feeding dolichol biosynthesis was resolved by confirming CPT catalyzes polyprenol chain elongation in the parasite.\",\n      \"evidence\": \"Metabolomics profiling plus confirmation of enzymatic activity in intraerythrocytic and gametocyte stages\",\n      \"pmids\": [\"32764679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution or mutagenesis of the purified protein\",\n        \"Chain-length specificity determinants not dissected\",\n        \"Subcellular localization of the enzyme not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To ask whether CPT output is developmentally controlled, polyprenol/dolichol profiles were tracked across stages, revealing stage-specific differences that imply regulated CPT activity.\",\n      \"evidence\": \"Metabolomics profiling across intraerythrocytic asexual and gametocyte developmental stages\",\n      \"pmids\": [\"32764679\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, single metabolomics method with no direct mechanistic dissection of CPT regulation\",\n        \"Transcriptional versus post-translational control of activity unresolved\",\n        \"Whether profile changes reflect CPT abundance or activity is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"To address the enzyme's quaternary organization, phylogenetic analysis predicted CPT is a catalytic subunit requiring an accessory subunit for a fully active heteromeric complex.\",\n      \"evidence\": \"Comparative/phylogenetic analysis; no direct Plasmodium experiment performed\",\n      \"pmids\": [\"40847593\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, with no experimental validation in Plasmodium\",\n        \"No CPT accessory subunit partner identified in Plasmodium\",\n        \"Complex stoichiometry and requirement for activity untested\"\n      ],\n      \"attribution\": []\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether CPT functions as a heteromeric enzyme in Plasmodium and the identity of any accessory subunit remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experimentally identified CPT accessory subunit\",\n        \"No structural or reconstitution data for the putative complex\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0045547\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019408\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfPPRD (polyprenol reductase; acts downstream on CPT product) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Produces polyprenols of 15\\u201319 isoprene units as the committed step of dolichol biosynthesis [#0]\",\n      \"Polyprenol/dolichol profile varies across intraerythrocytic asexual cycle and between asexual and gametocyte stages [#1]\",\n      \"Predicted catalytic subunit of a heteromeric cis-prenyltransferase requiring an unidentified accessory subunit [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0826400","name":null,"product":"cis-prenyltransferase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0704200","name":null,"product":"cis-prenyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1320600","name":null,"product":"cis-prenyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CPT","evaluation":null}