{"gene":"PF3D7_1455900","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2020,"finding":"PPRD (PF3D7_1455900) functions as an active polyprenol reductase in P. falciparum, catalyzing the reduction of polyprenol to dolichol as part of the dolichol biosynthesis pathway. Metabolomics profiling confirmed de novo biosynthesis of polyprenols and dolichols of 15–19 isoprene units and demonstrated that dolichol production occurs via polyprenol reduction by PfPPRD.","method":"Metabolomics profiling; enzymatic activity confirmation in P. falciparum intraerythrocytic stages","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — metabolomics combined with activity confirmation in parasite, single lab, two complementary approaches (lipid profiling + enzymatic activity assay)","pmids":["32764679"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PPRD (PF3D7_1455900)-dependent dolichol biosynthesis in P. falciparum produces a distinctive polyprenol and dolichol profile that changes across the intraerythrocytic asexual cycle and between asexual and gametocyte stages, indicating that PPRD activity (and thus cis-polyisoprenoid biosynthesis) is developmentally regulated.","method":"Metabolomics profiling across parasite developmental stages","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single metabolomics method, indirect inference of PPRD activity from lipid profiles rather than direct enzymatic measurement at each stage","pmids":["32764679"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PPRD (PF3D7_1455900) is an active polyprenol reductase in P. falciparum that catalyzes the reduction of polyprenol to dolichol (C75–C95, 15–19 isoprene units) as a key step in dolichol biosynthesis, with its activity (inferred from lipid profiles) appearing to vary across intraerythrocytic asexual and gametocyte developmental stages."},"narrative":{"mechanistic_narrative":"PPRD (PF3D7_1455900) is an active polyprenol reductase in Plasmodium falciparum that catalyzes the reduction of polyprenol to dolichol as a committed step in the parasite's dolichol biosynthesis pathway [PMID:32764679]. Metabolomics profiling of intraerythrocytic stages established de novo biosynthesis of polyprenols and dolichols of 15–19 isoprene units and demonstrated that dolichol is produced via PPRD-mediated polyprenol reduction [PMID:32764679]. Beyond this enzymatic assignment, no further mechanistic detail—structural model, catalytic residues, cofactor requirements, or protein partners—has been characterized for PPRD in the available corpus.","teleology":[{"year":2020,"claim":"It was unknown whether P. falciparum synthesizes dolichol de novo and which enzyme performs the polyprenol-to-dolichol reduction; identifying PPRD as the responsible reductase established the enzymatic basis of parasite dolichol biosynthesis.","evidence":"Metabolomics lipid profiling combined with enzymatic activity confirmation in P. falciparum intraerythrocytic stages","pmids":["32764679"],"confidence":"Medium","gaps":["No structural model, catalytic residues, or cofactor requirement defined for PPRD","Enzyme activity inferred from parasite lipid profiles rather than reconstituted with purified protein","No knockout/knockdown to establish essentiality or downstream glycosylation consequences"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether PPRD-dependent cis-polyisoprenoid production is constant or stage-specific was unresolved; distinct polyprenol/dolichol profiles across the asexual cycle and between asexual and gametocyte stages indicated developmental regulation of this pathway.","evidence":"Metabolomics profiling across P. falciparum developmental stages, with PPRD activity inferred from lipid profiles","pmids":["32764679"],"confidence":"Low","gaps":["PPRD activity inferred indirectly from lipid profiles rather than measured directly at each stage","Regulatory mechanism (transcriptional, post-translational) driving stage-specific activity unknown","Functional consequence of stage-specific dolichol levels not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The catalytic mechanism, cofactor dependence, structural basis, essentiality, and protein interaction context of PPRD remain uncharacterized.","evidence":"No further direct experimental evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No reconstitution with purified enzyme","No genetic essentiality data","No structural or interaction data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Catalyzes reduction of polyprenol to dolichol (C75–C95, 15–19 isoprene units) in P. falciparum [#0]","PPRD-dependent polyprenol/dolichol profile changes across the intraerythrocytic asexual cycle and between asexual and gametocyte stages, indicating developmentally regulated activity [#1]"]}},"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":["polyprenol reductase"],"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":["polyprenol reductase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3813,"output_tokens":664,"usd":0.0107,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5274,"output_tokens":1435,"usd":0.031123,"stage2_stop_reason":"end_turn"},"total_usd":0.041823,"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\": 2020,\n      \"finding\": \"PPRD (PF3D7_1455900) functions as an active polyprenol reductase in P. falciparum, catalyzing the reduction of polyprenol to dolichol as part of the dolichol biosynthesis pathway. Metabolomics profiling confirmed de novo biosynthesis of polyprenols and dolichols of 15–19 isoprene units and demonstrated that dolichol production occurs via polyprenol reduction by PfPPRD.\",\n      \"method\": \"Metabolomics profiling; enzymatic activity confirmation in P. falciparum intraerythrocytic stages\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — metabolomics combined with activity confirmation in parasite, single lab, two complementary approaches (lipid profiling + enzymatic activity assay)\",\n      \"pmids\": [\"32764679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PPRD (PF3D7_1455900)-dependent dolichol biosynthesis in P. falciparum produces a distinctive polyprenol and dolichol profile that changes across the intraerythrocytic asexual cycle and between asexual and gametocyte stages, indicating that PPRD activity (and thus cis-polyisoprenoid biosynthesis) is developmentally regulated.\",\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, indirect inference of PPRD activity from lipid profiles rather than direct enzymatic measurement at each stage\",\n      \"pmids\": [\"32764679\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PPRD (PF3D7_1455900) is an active polyprenol reductase in P. falciparum that catalyzes the reduction of polyprenol to dolichol (C75–C95, 15–19 isoprene units) as a key step in dolichol biosynthesis, with its activity (inferred from lipid profiles) appearing to vary across intraerythrocytic asexual and gametocyte developmental stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PPRD (PF3D7_1455900) is an active polyprenol reductase in Plasmodium falciparum that catalyzes the reduction of polyprenol to dolichol as a committed step in the parasite's dolichol biosynthesis pathway [#0]. Metabolomics profiling of intraerythrocytic stages established de novo biosynthesis of polyprenols and dolichols of 15\\u201319 isoprene units and demonstrated that dolichol is produced via PPRD-mediated polyprenol reduction [#0]. Beyond this enzymatic assignment, no further mechanistic detail\\u2014structural model, catalytic residues, cofactor requirements, or protein partners\\u2014has been characterized for PPRD in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"It was unknown whether P. falciparum synthesizes dolichol de novo and which enzyme performs the polyprenol-to-dolichol reduction; identifying PPRD as the responsible reductase established the enzymatic basis of parasite dolichol biosynthesis.\",\n      \"evidence\": \"Metabolomics lipid profiling combined with enzymatic activity confirmation in P. falciparum intraerythrocytic stages\",\n      \"pmids\": [\"32764679\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model, catalytic residues, or cofactor requirement defined for PPRD\",\n        \"Enzyme activity inferred from parasite lipid profiles rather than reconstituted with purified protein\",\n        \"No knockout/knockdown to establish essentiality or downstream glycosylation consequences\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether PPRD-dependent cis-polyisoprenoid production is constant or stage-specific was unresolved; distinct polyprenol/dolichol profiles across the asexual cycle and between asexual and gametocyte stages indicated developmental regulation of this pathway.\",\n      \"evidence\": \"Metabolomics profiling across P. falciparum developmental stages, with PPRD activity inferred from lipid profiles\",\n      \"pmids\": [\"32764679\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"PPRD activity inferred indirectly from lipid profiles rather than measured directly at each stage\",\n        \"Regulatory mechanism (transcriptional, post-translational) driving stage-specific activity unknown\",\n        \"Functional consequence of stage-specific dolichol levels not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic mechanism, cofactor dependence, structural basis, essentiality, and protein interaction context of PPRD remain uncharacterized.\",\n      \"evidence\": \"No further direct experimental evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution with purified enzyme\",\n        \"No genetic essentiality data\",\n        \"No structural or interaction data\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0102965\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019408\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Catalyzes reduction of polyprenol to dolichol (C75\\u2013C95, 15\\u201319 isoprene units) in P. falciparum [#0]\",\n      \"PPRD-dependent polyprenol/dolichol profile changes across the intraerythrocytic asexual cycle and between asexual and gametocyte stages, indicating developmentally regulated activity [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1455900","name":null,"product":"polyprenol reductase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1319600","name":null,"product":"polyprenol reductase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1225900","name":null,"product":"polyprenol reductase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PPRD","evaluation":null}