{"gene":"PF3D7_1014000","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2013,"finding":"P. falciparum GDP-L-fucose synthase (FS; PF3D7_1014000) is enzymatically active in vitro, demonstrating that the de novo GDP-fucose biosynthetic pathway (bioconversion of GDP-mannose) is functional in the parasite.","method":"In vitro enzymatic assay of recombinant FS; LC-MS/MS quantification of sugar nucleotide pools in intraerythrocytic stages","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro activity assay established enzymatic function, but performed by a single lab with no mutagenesis or structural validation","pmids":["23615908"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Epitope-tagged FS (PF3D7_1014000) expressed in transgenic P. falciparum 3D7 parasites localizes to the cytoplasm during the intraerythrocytic developmental cycle.","method":"Fluorescence microscopy of epitope-tagged FS expressed in transgenic 3D7 parasites","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — direct localization by fluorescence microscopy in transgenic parasites, single lab, no functional consequence explicitly linked to localization","pmids":["23615908"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2016,"finding":"Disruption of the GDP-fucose de novo pathway (via PfGMD knockout) completely abolished UEA-I lectin labelling but did not eliminate the GDP-fucose pool, suggesting an alternative mechanism maintains GDP-fucose independent of the GMD–FS (PF3D7_1014000) de novo route; the de novo pathway is not essential for asexual blood-stage growth or invasion in culture.","method":"Generation of PfGMD null mutant; LC-MS/MS detection of GDP-fucose; UEA-I lectin labelling; parasite growth and invasion assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic disruption of the upstream partner with multiple orthogonal readouts (metabolomics, lectin labelling, growth assay), single lab; finding is about the pathway containing FS rather than FS itself directly","pmids":["27849032"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1014000 (FS) encodes a cytoplasm-localised GDP-L-fucose synthase that is enzymatically active in vitro and participates in the de novo conversion of GDP-mannose to GDP-fucose in P. falciparum intraerythrocytic stages, but this pathway is dispensable for asexual blood-stage growth and an alternative mechanism can sustain the intracellular GDP-fucose pool when the pathway is disrupted."},"narrative":{"mechanistic_narrative":"PF3D7_1014000 (FS) encodes a GDP-L-fucose synthase that catalyzes the de novo conversion of GDP-mannose to GDP-fucose in Plasmodium falciparum, and recombinant enzyme is catalytically active in vitro, establishing that this branch of the de novo GDP-fucose biosynthetic pathway is functional in the parasite [PMID:23615908]. Epitope-tagged FS localizes to the cytoplasm of intraerythrocytic-stage parasites [PMID:23615908]. Genetic disruption of the upstream pathway enzyme PfGMD abolishes UEA-I lectin labelling yet does not eliminate the intracellular GDP-fucose pool, and the de novo pathway is dispensable for asexual blood-stage growth and invasion, indicating an alternative route can sustain GDP-fucose independently of the GMD–FS de novo pathway [PMID:27849032]. Beyond its in vitro activity, cytoplasmic localization, and its non-essential role in the de novo pathway, no further mechanistic detail for FS — including structural determinants, catalytic-residue mutagenesis, or its physiological fucosylation targets — has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Whether P. falciparum possesses a functional de novo GDP-fucose biosynthetic route was unknown; demonstrating that FS is catalytically active established the parasite encodes an operative GDP-mannose-to-GDP-fucose conversion step.","evidence":"In vitro enzymatic assay of recombinant FS with LC-MS/MS quantification of sugar-nucleotide pools in intraerythrocytic stages","pmids":["23615908"],"confidence":"Medium","gaps":["No mutagenesis of catalytic residues to confirm the assigned activity","No structural model of the enzyme","In vitro activity not linked to an in vivo fucosylation product"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"The subcellular compartment in which FS acts was undefined; localizing epitope-tagged FS placed the enzyme in the cytoplasm during the intraerythrocytic cycle, defining where de novo GDP-fucose synthesis occurs.","evidence":"Fluorescence microscopy of epitope-tagged FS in transgenic 3D7 parasites","pmids":["23615908"],"confidence":"Medium","gaps":["Tagging may not reflect endogenous localization","No functional consequence tied to cytoplasmic localization","Localization across other life-cycle stages not assessed"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2016,"claim":"Whether the GMD–FS de novo pathway is the sole and essential source of parasite GDP-fucose was untested; disrupting the upstream enzyme showed the de novo route is dispensable for blood-stage growth and that an alternative mechanism maintains the GDP-fucose pool.","evidence":"PfGMD null mutant with LC-MS/MS detection of GDP-fucose, UEA-I lectin labelling, and growth/invasion assays","pmids":["27849032"],"confidence":"Medium","gaps":["The alternative GDP-fucose source (e.g. a salvage route) was not identified","FS itself was not directly knocked out; the finding rests on disruption of the upstream partner PfGMD","Role of the pathway in non-asexual stages not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological targets of GDP-fucose-dependent fucosylation and the identity of the alternative pathway that sustains the GDP-fucose pool when de novo synthesis is disrupted remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No fucosylated glycoconjugate or protein target of FS-derived GDP-fucose identified","Alternative (salvage) route maintaining GDP-fucose uncharacterized","No direct genetic knockout of FS reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFGMD (GDP-MANNOSE 4,6-DEHYDRATASE; UPSTREAM DE NOVO PATHWAY ENZYME)"],"other_free_text":["De novo GDP-fucose pathway is dispensable for asexual blood-stage growth and invasion [#2]","An alternative mechanism sustains the GDP-fucose pool independent of the GMD-FS de novo route [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"1374032","id":"PMC_1374032","title":"Apparent lack of N-glycosylation in the asexual intraerythrocytic stage of Plasmodium falciparum.","date":"1992","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1374032","citation_count":110,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GDP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23615908","id":"PMC_23615908","title":"Biosynthesis of GDP-fucose and other sugar nucleotides in the blood stages of Plasmodium falciparum.","date":"2013","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23615908","citation_count":36,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GDP-L-fucose synthase","GDP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27849032","id":"PMC_27849032","title":"The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27849032","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GDP-L-fucose synthase","GDP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4588,"output_tokens":901,"usd":0.01364,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5639,"output_tokens":1918,"usd":0.038073,"stage2_stop_reason":"end_turn"},"total_usd":0.051713,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"P. falciparum GDP-L-fucose synthase (FS; PF3D7_1014000) is enzymatically active in vitro, demonstrating that the de novo GDP-fucose biosynthetic pathway (bioconversion of GDP-mannose) is functional in the parasite.\",\n      \"method\": \"In vitro enzymatic assay of recombinant FS; LC-MS/MS quantification of sugar nucleotide pools in intraerythrocytic stages\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro activity assay established enzymatic function, but performed by a single lab with no mutagenesis or structural validation\",\n      \"pmids\": [\"23615908\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Epitope-tagged FS (PF3D7_1014000) expressed in transgenic P. falciparum 3D7 parasites localizes to the cytoplasm during the intraerythrocytic developmental cycle.\",\n      \"method\": \"Fluorescence microscopy of epitope-tagged FS expressed in transgenic 3D7 parasites\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — direct localization by fluorescence microscopy in transgenic parasites, single lab, no functional consequence explicitly linked to localization\",\n      \"pmids\": [\"23615908\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Disruption of the GDP-fucose de novo pathway (via PfGMD knockout) completely abolished UEA-I lectin labelling but did not eliminate the GDP-fucose pool, suggesting an alternative mechanism maintains GDP-fucose independent of the GMD–FS (PF3D7_1014000) de novo route; the de novo pathway is not essential for asexual blood-stage growth or invasion in culture.\",\n      \"method\": \"Generation of PfGMD null mutant; LC-MS/MS detection of GDP-fucose; UEA-I lectin labelling; parasite growth and invasion assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic disruption of the upstream partner with multiple orthogonal readouts (metabolomics, lectin labelling, growth assay), single lab; finding is about the pathway containing FS rather than FS itself directly\",\n      \"pmids\": [\"27849032\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1014000 (FS) encodes a cytoplasm-localised GDP-L-fucose synthase that is enzymatically active in vitro and participates in the de novo conversion of GDP-mannose to GDP-fucose in P. falciparum intraerythrocytic stages, but this pathway is dispensable for asexual blood-stage growth and an alternative mechanism can sustain the intracellular GDP-fucose pool when the pathway is disrupted.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_1014000 (FS) encodes a GDP-L-fucose synthase that catalyzes the de novo conversion of GDP-mannose to GDP-fucose in Plasmodium falciparum, and recombinant enzyme is catalytically active in vitro, establishing that this branch of the de novo GDP-fucose biosynthetic pathway is functional in the parasite [#0]. Epitope-tagged FS localizes to the cytoplasm of intraerythrocytic-stage parasites [#1]. Genetic disruption of the upstream pathway enzyme PfGMD abolishes UEA-I lectin labelling yet does not eliminate the intracellular GDP-fucose pool, and the de novo pathway is dispensable for asexual blood-stage growth and invasion, indicating an alternative route can sustain GDP-fucose independently of the GMD–FS de novo pathway [#2]. Beyond its in vitro activity, cytoplasmic localization, and its non-essential role in the de novo pathway, no further mechanistic detail for FS — including structural determinants, catalytic-residue mutagenesis, or its physiological fucosylation targets — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether P. falciparum possesses a functional de novo GDP-fucose biosynthetic route was unknown; demonstrating that FS is catalytically active established the parasite encodes an operative GDP-mannose-to-GDP-fucose conversion step.\",\n      \"evidence\": \"In vitro enzymatic assay of recombinant FS with LC-MS/MS quantification of sugar-nucleotide pools in intraerythrocytic stages\",\n      \"pmids\": [\"23615908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mutagenesis of catalytic residues to confirm the assigned activity\",\n        \"No structural model of the enzyme\",\n        \"In vitro activity not linked to an in vivo fucosylation product\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"The subcellular compartment in which FS acts was undefined; localizing epitope-tagged FS placed the enzyme in the cytoplasm during the intraerythrocytic cycle, defining where de novo GDP-fucose synthesis occurs.\",\n      \"evidence\": \"Fluorescence microscopy of epitope-tagged FS in transgenic 3D7 parasites\",\n      \"pmids\": [\"23615908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Tagging may not reflect endogenous localization\",\n        \"No functional consequence tied to cytoplasmic localization\",\n        \"Localization across other life-cycle stages not assessed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether the GMD–FS de novo pathway is the sole and essential source of parasite GDP-fucose was untested; disrupting the upstream enzyme showed the de novo route is dispensable for blood-stage growth and that an alternative mechanism maintains the GDP-fucose pool.\",\n      \"evidence\": \"PfGMD null mutant with LC-MS/MS detection of GDP-fucose, UEA-I lectin labelling, and growth/invasion assays\",\n      \"pmids\": [\"27849032\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The alternative GDP-fucose source (e.g. a salvage route) was not identified\",\n        \"FS itself was not directly knocked out; the finding rests on disruption of the upstream partner PfGMD\",\n        \"Role of the pathway in non-asexual stages not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological targets of GDP-fucose-dependent fucosylation and the identity of the alternative pathway that sustains the GDP-fucose pool when de novo synthesis is disrupted remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No fucosylated glycoconjugate or protein target of FS-derived GDP-fucose identified\",\n        \"Alternative (salvage) route maintaining GDP-fucose uncharacterized\",\n        \"No direct genetic knockout of FS reported\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0050577\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042351\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfGMD (GDP-mannose 4,6-dehydratase; upstream de novo pathway enzyme)\"],\n    \"other_free_text\": [\n      \"De novo GDP-fucose pathway is dispensable for asexual blood-stage growth and invasion [#2]\",\n      \"An alternative mechanism sustains the GDP-fucose pool independent of the GMD-FS de novo route [#2]\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1014000","name":null,"product":"GDP-L-fucose synthase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1212400","name":null,"product":"GDP-L-fucose synthase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0813800","name":null,"product":"GDP-L-fucose synthase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"FS","evaluation":null}