{"gene":"PF3D7_1022800","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2005,"finding":"The E. coli IspG protein (ortholog of PF3D7_1022800) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in the non-mevalonate isoprenoid biosynthesis pathway. The enzyme requires an iron-sulfur cluster (containing ~2.4 Fe and ~4.4 S per subunit), is activated by Mn2+, inactivated by EDTA, uses flavodoxin/flavodoxin reductase/NADPH as the physiological electron donor system, and three conserved cysteine residues are essential for catalytic activity and FeS cluster retention. The Plasmodium falciparum IspG contains an insert of ~170–320 amino acids relative to eubacterial orthologs.","method":"Affinity chromatography purification under anaerobic conditions, radiochemical and 13C NMR enzymatic assays, site-directed mutagenesis of conserved cysteines, metal content analysis, pH/inhibitor profiling, sequence comparison","journal":"The Journal of organic chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — rigorous in vitro reconstitution and mutagenesis, but performed on E. coli ortholog; Plasmodium falciparum findings limited to sequence comparison only","pmids":["16268586"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"The P. vivax ortholog of ISPG (PF3D7_1022800), a 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, localizes to the apicoplast as demonstrated by immune-localization on infected blood smears from clinical patients. Biochemical reconstitution and in silico docking indicate that [4Fe-4S] clusters are required for enzyme activity.","method":"Immune-localization on P. vivax-infected blood smears, biochemical reconstitution of FeS clusters, in silico docking","journal":"International journal of biological macromolecules","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, apicoplast localization by immunostaining only, FeS cluster importance supported by in silico docking and reconstitution but not by mutagenesis or functional assay","pmids":["28007455"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2019,"finding":"Fe-S clusters assembled on the scaffold protein PvSufA (from the SUF pathway) can be transferred in vitro to apo-PvIspG (the P. vivax ortholog of PF3D7_1022800), demonstrating that ISPG is a downstream recipient of FeS clusters from the SUF biogenesis pathway in the apicoplast.","method":"In vitro Fe-S cluster transfer assay using P. vivax clinical isolate proteins","journal":"Experimental parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single in vitro transfer assay, no complementary structural or mutagenesis data","pmids":["30721667"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2022,"finding":"Genetic deletion of ISPG (PF3D7_1022800) in P. falciparum (using an apicoplast metabolic bypass line, PfMev) established that it is essential for parasite survival in blood-stage parasites but not required for apicoplast organelle maintenance. ISPG obtains its FeS cofactor redundantly from either SufA or NfuApi transfer proteins.","method":"Conditional genetic deletion in PfMev apicoplast bypass line, phenotypic assessment of parasite survival and apicoplast maintenance, double deletion of SufA and NfuApi showing synthetic lethality","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with defined cellular phenotype in a well-controlled bypass system, two orthogonal genetic deletions (individual and double) supporting the pathway placement","pmids":["35164549"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"ISPG (PF3D7_1022800) is a [4Fe-4S]-dependent enzyme in the apicoplast of Plasmodium that catalyzes the penultimate step of the MEP isoprenoid biosynthesis pathway (conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate to 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate), is essential for blood-stage parasite survival (but not apicoplast maintenance), receives its FeS cofactor redundantly from either SufA or NfuApi transfer proteins, and depends on the Fd/FNR redox system as a source of reducing power."},"narrative":{"mechanistic_narrative":"ISPG (PF3D7_1022800) is the Plasmodium 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, a [4Fe-4S] cluster-dependent enzyme that catalyzes the penultimate step of the non-mevalonate (MEP) isoprenoid biosynthesis pathway, converting 2-C-methyl-D-erythritol 2,4-cyclodiphosphate to 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate, as established for the E. coli ortholog through in vitro reconstitution, metal analysis, and cysteine mutagenesis [PMID:16268586]. In Plasmodium the enzyme localizes to the apicoplast, where FeS-cluster–dependent activity has been reconstituted for the P. vivax ortholog [PMID:28007455], and it receives its [4Fe-4S] cofactor from the apicoplast SUF biogenesis pathway, accepting clusters transferred from the scaffold protein SufA in vitro [PMID:30721667]. Conditional genetic deletion in P. falciparum showed that ISPG is essential for blood-stage survival yet dispensable for apicoplast organelle maintenance, and that it obtains its cofactor redundantly from either SufA or NfuApi, since only their combined loss is lethal [PMID:35164549]. The Plasmodium falciparum enzyme carries a large parasite-specific insert of ~170–320 residues relative to eubacterial orthologs [PMID:16268586], whose functional significance has not been characterized in the available corpus.","teleology":[{"year":2005,"claim":"Establishing the catalytic identity of the IspG family answered what reaction and cofactor requirements define this enzyme, providing the mechanistic template later applied to the Plasmodium protein.","evidence":"Anaerobic purification, radiochemical and 13C NMR assays, cysteine mutagenesis and metal analysis on the E. coli ortholog, with sequence comparison to P. falciparum","pmids":["16268586"],"confidence":"Medium","gaps":["Catalytic activity and cofactor requirements demonstrated on the E. coli ortholog, not on the Plasmodium enzyme","Function of the ~170–320 residue Plasmodium-specific insert not addressed","Physiological electron donor in Plasmodium not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Localizing the Plasmodium ortholog established where the enzyme acts and confirmed its dependence on [4Fe-4S] clusters, connecting it to apicoplast metabolism.","evidence":"Immune-localization on P. vivax-infected clinical blood smears plus in vitro FeS reconstitution and in silico docking","pmids":["28007455"],"confidence":"Low","gaps":["Apicoplast localization by immunostaining only, no orthogonal tag or fractionation","FeS requirement supported by docking and reconstitution but not by mutagenesis or functional enzyme assay"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2019,"claim":"Demonstrating cluster transfer from SufA to apo-ISPG answered how the enzyme acquires its cofactor within the apicoplast, placing it downstream of the SUF biogenesis machinery.","evidence":"In vitro Fe-S cluster transfer assay using P. vivax clinical isolate proteins","pmids":["30721667"],"confidence":"Low","gaps":["Single in vitro transfer assay without structural or mutagenesis corroboration","Does not establish in vivo dependence or exclusivity of SufA as donor"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2022,"claim":"Conditional deletion resolved whether ISPG is essential and how its cofactor delivery is organized, showing it is required for blood-stage survival independent of apicoplast maintenance and served redundantly by two carrier proteins.","evidence":"Conditional genetic deletion in the PfMev apicoplast bypass line with individual and double SufA/NfuApi deletions in P. falciparum","pmids":["35164549"],"confidence":"Medium","gaps":["In vivo enzymatic output and metabolite flux not directly measured","Structural basis of redundant cofactor loading by SufA versus NfuApi not defined","Role of the Fd/FNR redox system in supplying reducing power not tested here"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological electron donor for Plasmodium ISPG and the function of its parasite-specific insert remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct demonstration of the in vivo reductant (Fd/FNR) driving Plasmodium ISPG catalysis","Functional and structural role of the ~170–320 residue insert uncharacterized","No structure of the Plasmodium enzyme or its cofactor-loaded state"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["SUFA (FES CLUSTER DONOR)","NFUAPI (FES CLUSTER DONOR)"],"other_free_text":["Catalyzes the penultimate MEP-pathway step: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate -> 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate [#0].","Essential for P. falciparum blood-stage survival but dispensable for apicoplast maintenance [#3].","Receives its [4Fe-4S] cofactor redundantly from either SufA or NfuApi (synthetic lethality upon double deletion) [#3].","P. falciparum ISPG carries a ~170-320 residue insert relative to eubacterial orthologs; function uncharacterized [#0].","E. coli ortholog uses flavodoxin/flavodoxin reductase/NADPH as electron donor and is activated by Mn2+; not tested in Plasmodium [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16268586","id":"PMC_16268586","title":"Biosynthesis of isoprenoids. purification and properties of IspG protein from Escherichia coli.","date":"2005","source":"The Journal of organic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16268586","citation_count":38,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISPG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35164549","id":"PMC_35164549","title":"Roles of Ferredoxin-Dependent Proteins in the Apicoplast of Plasmodium falciparum Parasites.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35164549","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISPG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28007455","id":"PMC_28007455","title":"Characterization of 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG) from Plasmodium vivax and it's potential as an antimalarial drug target.","date":"2016","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/28007455","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISPG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30721667","id":"PMC_30721667","title":"Functional analysis of iron-sulfur cluster biogenesis (SUF pathway) from Plasmodium vivax clinical isolates.","date":"2019","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/30721667","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISPG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35463632","id":"PMC_35463632","title":"Apicoplast Journey and Its Essentiality as a Compartment for Malaria Parasite Survival.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35463632","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ISPG"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5319,"output_tokens":1454,"usd":0.018884,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6413,"output_tokens":2578,"usd":0.048258,"stage2_stop_reason":"end_turn"},"total_usd":0.067142,"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\": 2005,\n      \"finding\": \"The E. coli IspG protein (ortholog of PF3D7_1022800) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in the non-mevalonate isoprenoid biosynthesis pathway. The enzyme requires an iron-sulfur cluster (containing ~2.4 Fe and ~4.4 S per subunit), is activated by Mn2+, inactivated by EDTA, uses flavodoxin/flavodoxin reductase/NADPH as the physiological electron donor system, and three conserved cysteine residues are essential for catalytic activity and FeS cluster retention. The Plasmodium falciparum IspG contains an insert of ~170–320 amino acids relative to eubacterial orthologs.\",\n      \"method\": \"Affinity chromatography purification under anaerobic conditions, radiochemical and 13C NMR enzymatic assays, site-directed mutagenesis of conserved cysteines, metal content analysis, pH/inhibitor profiling, sequence comparison\",\n      \"journal\": \"The Journal of organic chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — rigorous in vitro reconstitution and mutagenesis, but performed on E. coli ortholog; Plasmodium falciparum findings limited to sequence comparison only\",\n      \"pmids\": [\"16268586\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The P. vivax ortholog of ISPG (PF3D7_1022800), a 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, localizes to the apicoplast as demonstrated by immune-localization on infected blood smears from clinical patients. Biochemical reconstitution and in silico docking indicate that [4Fe-4S] clusters are required for enzyme activity.\",\n      \"method\": \"Immune-localization on P. vivax-infected blood smears, biochemical reconstitution of FeS clusters, in silico docking\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, apicoplast localization by immunostaining only, FeS cluster importance supported by in silico docking and reconstitution but not by mutagenesis or functional assay\",\n      \"pmids\": [\"28007455\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium vivax\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Fe-S clusters assembled on the scaffold protein PvSufA (from the SUF pathway) can be transferred in vitro to apo-PvIspG (the P. vivax ortholog of PF3D7_1022800), demonstrating that ISPG is a downstream recipient of FeS clusters from the SUF biogenesis pathway in the apicoplast.\",\n      \"method\": \"In vitro Fe-S cluster transfer assay using P. vivax clinical isolate proteins\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single in vitro transfer assay, no complementary structural or mutagenesis data\",\n      \"pmids\": [\"30721667\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium vivax\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Genetic deletion of ISPG (PF3D7_1022800) in P. falciparum (using an apicoplast metabolic bypass line, PfMev) established that it is essential for parasite survival in blood-stage parasites but not required for apicoplast organelle maintenance. ISPG obtains its FeS cofactor redundantly from either SufA or NfuApi transfer proteins.\",\n      \"method\": \"Conditional genetic deletion in PfMev apicoplast bypass line, phenotypic assessment of parasite survival and apicoplast maintenance, double deletion of SufA and NfuApi showing synthetic lethality\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with defined cellular phenotype in a well-controlled bypass system, two orthogonal genetic deletions (individual and double) supporting the pathway placement\",\n      \"pmids\": [\"35164549\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ISPG (PF3D7_1022800) is a [4Fe-4S]-dependent enzyme in the apicoplast of Plasmodium that catalyzes the penultimate step of the MEP isoprenoid biosynthesis pathway (conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate to 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate), is essential for blood-stage parasite survival (but not apicoplast maintenance), receives its FeS cofactor redundantly from either SufA or NfuApi transfer proteins, and depends on the Fd/FNR redox system as a source of reducing power.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ISPG (PF3D7_1022800) is the Plasmodium 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, a [4Fe-4S] cluster-dependent enzyme that catalyzes the penultimate step of the non-mevalonate (MEP) isoprenoid biosynthesis pathway, converting 2-C-methyl-D-erythritol 2,4-cyclodiphosphate to 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate, as established for the E. coli ortholog through in vitro reconstitution, metal analysis, and cysteine mutagenesis [#0]. In Plasmodium the enzyme localizes to the apicoplast, where FeS-cluster–dependent activity has been reconstituted for the P. vivax ortholog [#1], and it receives its [4Fe-4S] cofactor from the apicoplast SUF biogenesis pathway, accepting clusters transferred from the scaffold protein SufA in vitro [#2]. Conditional genetic deletion in P. falciparum showed that ISPG is essential for blood-stage survival yet dispensable for apicoplast organelle maintenance, and that it obtains its cofactor redundantly from either SufA or NfuApi, since only their combined loss is lethal [#3]. The Plasmodium falciparum enzyme carries a large parasite-specific insert of ~170–320 residues relative to eubacterial orthologs [#0], whose functional significance has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Establishing the catalytic identity of the IspG family answered what reaction and cofactor requirements define this enzyme, providing the mechanistic template later applied to the Plasmodium protein.\",\n      \"evidence\": \"Anaerobic purification, radiochemical and 13C NMR assays, cysteine mutagenesis and metal analysis on the E. coli ortholog, with sequence comparison to P. falciparum\",\n      \"pmids\": [\"16268586\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Catalytic activity and cofactor requirements demonstrated on the E. coli ortholog, not on the Plasmodium enzyme\",\n        \"Function of the ~170–320 residue Plasmodium-specific insert not addressed\",\n        \"Physiological electron donor in Plasmodium not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Localizing the Plasmodium ortholog established where the enzyme acts and confirmed its dependence on [4Fe-4S] clusters, connecting it to apicoplast metabolism.\",\n      \"evidence\": \"Immune-localization on P. vivax-infected clinical blood smears plus in vitro FeS reconstitution and in silico docking\",\n      \"pmids\": [\"28007455\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Apicoplast localization by immunostaining only, no orthogonal tag or fractionation\",\n        \"FeS requirement supported by docking and reconstitution but not by mutagenesis or functional enzyme assay\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrating cluster transfer from SufA to apo-ISPG answered how the enzyme acquires its cofactor within the apicoplast, placing it downstream of the SUF biogenesis machinery.\",\n      \"evidence\": \"In vitro Fe-S cluster transfer assay using P. vivax clinical isolate proteins\",\n      \"pmids\": [\"30721667\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single in vitro transfer assay without structural or mutagenesis corroboration\",\n        \"Does not establish in vivo dependence or exclusivity of SufA as donor\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Conditional deletion resolved whether ISPG is essential and how its cofactor delivery is organized, showing it is required for blood-stage survival independent of apicoplast maintenance and served redundantly by two carrier proteins.\",\n      \"evidence\": \"Conditional genetic deletion in the PfMev apicoplast bypass line with individual and double SufA/NfuApi deletions in P. falciparum\",\n      \"pmids\": [\"35164549\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"In vivo enzymatic output and metabolite flux not directly measured\",\n        \"Structural basis of redundant cofactor loading by SufA versus NfuApi not defined\",\n        \"Role of the Fd/FNR redox system in supplying reducing power not tested here\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological electron donor for Plasmodium ISPG and the function of its parasite-specific insert remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct demonstration of the in vivo reductant (Fd/FNR) driving Plasmodium ISPG catalysis\",\n        \"Functional and structural role of the ~170–320 residue insert uncharacterized\",\n        \"No structure of the Plasmodium enzyme or its cofactor-loaded state\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0046429\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0051539\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0051537\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019288\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0016226\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"SufA (FeS cluster donor)\",\n      \"NfuApi (FeS cluster donor)\"\n    ],\n    \"other_free_text\": [\n      \"Catalyzes the penultimate MEP-pathway step: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate -> 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate [#0].\",\n      \"Essential for P. falciparum blood-stage survival but dispensable for apicoplast maintenance [#3].\",\n      \"Receives its [4Fe-4S] cofactor redundantly from either SufA or NfuApi (synthetic lethality upon double deletion) [#3].\",\n      \"P. falciparum ISPG carries a ~170-320 residue insert relative to eubacterial orthologs; function uncharacterized [#0].\",\n      \"E. coli ortholog uses flavodoxin/flavodoxin reductase/NADPH as electron donor and is activated by Mn2+; not tested in Plasmodium [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1022800","name":null,"product":"4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ferredoxin)","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0507000","name":null,"product":"4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ferredoxin), putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0607100","name":null,"product":"4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (ferredoxin), putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ISPG","evaluation":null}