{"gene":"PF3D7_0709700","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2017,"finding":"PARE (PF3D7_0709700) is a functional esterase capable of hydrolyzing pepstatin esters and de-esterifying the open-source antimalarial MMV011438 in vitro, thereby activating these prodrugs; mutations in PARE confer resistance to pepstatin esters and MMV011438 in P. falciparum.","method":"In vitro resistance selection with whole-genome sequencing of resistant mutants; recombinant PARE enzymatic assay with pepstatin esters and MMV011438 as substrates","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — recombinant enzyme activity demonstrated in vitro plus orthogonal resistance genetics (mutant selection + sequencing), multiple substrates tested, single rigorous study","pmids":["28106035"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Mutations in PARE (PF3D7_0709700) mediate in vitro resistance to the lindenane sesquiterpenoid dimer chlorajaponilide C (>250-fold EC50 increase), indicating that PARE-mediated esterase activity is required for the potency of this compound class, though not all related sesquiterpenoid dimers depend on PARE.","method":"In vitro resistance selection, whole-genome sequencing of resistant clones, structure-resistance relationship analysis across compound series","journal":"ACS infectious diseases","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — resistance genetics (selection + WGS) with SAR analysis across multiple compounds, single lab","pmids":["32970404"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"PARE (PF3D7_0709700) is detected as an active serine hydrolase in the asexual erythrocytic stage of P. falciparum using a fluorophosphonate-based affinity capture probe coupled to mass spectrometry, confirming active-site serine hydrolase activity in the native parasite.","method":"Fluorophosphonate-based activity-based protein profiling (ABPP) with mass spectrometry","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — chemoproteomic ABPP directly demonstrates active serine hydrolase activity in situ, but single lab and single method for this specific protein","pmids":["31772212"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"The PARE (PF3D7_0709700) locus is expressed throughout the intraerythrocytic cycle, is not essential for parasite viability, and is highly conserved across P. falciparum strains, as demonstrated by successful disruption of the locus by CRISPR-based mNeonGreen reporter insertion with negligible fitness defect.","method":"CRISPR-based gene disruption/tagging, competitive growth assay (fitness measurement), fluorescence reporter expression monitoring","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct functional genetic experiment (locus disruption with fitness readout), single lab, single method","pmids":["36189342"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"Dd2"}]},{"year":2025,"finding":"PARE (PF3D7_0709700) is a membrane-associated enzyme with a substantial presence at the parasite periphery and contributes to lysophosphatidylcholine (LPC) hydrolysis; loss of PARE alone did not affect fatty acid scavenging from LPC, but when combined with loss of XL2 and XLH4 (triple knockdown), the parasites were impaired in scavenging both choline and fatty acids from LPC and could not complete a replication cycle when LPC was the sole exogenous fatty acid source.","method":"Genetic knockdown (PARE alone and in combination with XL2/XLH4), growth assays in defined media with LPC as sole fatty acid source, subcellular localization by direct imaging/fractionation","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis via triple loss-of-function with specific metabolic readout, direct membrane/peripheral localization established, single lab with multiple orthogonal approaches","pmids":["41043577"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PARE (PF3D7_0709700) is a membrane-associated serine hydrolase/esterase expressed throughout the P. falciparum intraerythrocytic cycle that localizes to the parasite periphery, where it hydrolyzes ester bonds in lysophosphatidylcholine as a minor contributor to fatty acid scavenging alongside XL2 and XLH4, and can also activate esterified prodrugs (pepstatin esters, MMV011438, chlorajaponilide C) by de-esterification, such that mutations in PARE confer resistance to these compounds while disruption of the locus alone causes negligible fitness defect."},"narrative":{"mechanistic_narrative":"PARE (PF3D7_0709700) is a membrane-associated serine hydrolase expressed throughout the P. falciparum intraerythrocytic cycle whose native de-esterification activity is co-opted both for lipid metabolism and for antimalarial prodrug activation [PMID:28106035, PMID:41043577]. It behaves as a bona fide active-site serine hydrolase in the asexual blood stage, where it is captured by fluorophosphonate activity-based probes in situ [PMID:31772212], and it hydrolyzes ester bonds in a range of substrates in vitro, activating the esterified prodrugs pepstatin esters and MMV011438 through de-esterification [PMID:28106035]. Because compound potency depends on this activation step, loss-of-function mutations in PARE confer resistance to pepstatin esters and MMV011438 [PMID:28106035] and to the lindenane sesquiterpenoid dimer chlorajaponilide C [PMID:32970404]. Biologically, PARE localizes to the parasite periphery and contributes to hydrolysis of lysophosphatidylcholine (LPC); it is a minor, redundant player in this process, since its disruption alone causes negligible fitness defect and does not impair fatty acid scavenging, whereas combined loss of PARE with XL2 and XLH4 blocks scavenging of choline and fatty acids from LPC and prevents replication when LPC is the sole exogenous fatty acid source [PMID:36189342, PMID:41043577]. Beyond these roles in LPC hydrolysis and prodrug activation, no further mechanistic detail for PARE has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Establishing that a parasite esterase can activate esterified antimalarials answered how certain prodrugs become active and revealed a genetic route to resistance.","evidence":"In vitro resistance selection with whole-genome sequencing plus recombinant enzyme assays on pepstatin esters and MMV011438 in P. falciparum","pmids":["28106035"],"confidence":"High","gaps":["Native physiological substrate not defined at this stage","Structural basis of ester recognition not resolved","Subcellular location not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Demonstrating that PARE is labeled by a serine-hydrolase active-site probe in intact parasites confirmed that the enzyme is catalytically active in its native context, not just as a recombinant protein.","evidence":"Fluorophosphonate-based activity-based protein profiling with mass spectrometry in asexual erythrocytic-stage P. falciparum","pmids":["31772212"],"confidence":"Medium","gaps":["Single method and single lab for this protein","Does not identify endogenous substrate","Activity not quantified against specific lipids"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Extending resistance genetics to a structurally distinct compound class showed the prodrug-activation role generalizes, while SAR indicated the dependence is compound-specific.","evidence":"In vitro resistance selection, whole-genome sequencing, and structure-resistance analysis across chlorajaponilide-related sesquiterpenoid dimers in P. falciparum","pmids":["32970404"],"confidence":"Medium","gaps":["Direct enzymatic de-esterification of chlorajaponilide C not shown in vitro","Basis for which dimers require PARE not molecularly defined","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Genetic disruption clarified that PARE is dispensable for parasite viability, framing its endogenous role as non-essential and redundant.","evidence":"CRISPR-based mNeonGreen reporter insertion/disruption with competitive fitness assay and expression profiling in P. falciparum Dd2","pmids":["36189342"],"confidence":"Medium","gaps":["Endogenous function not identified by disruption alone","Redundant partners not tested here","Single method"],"attribution":[{"species":"Plasmodium falciparum","strain":"Dd2"}]},{"year":2025,"claim":"Combining localization and epistasis assigned PARE a concrete but redundant physiological role in lysophosphatidylcholine hydrolysis at the parasite periphery.","evidence":"Single and combinatorial knockdown of PARE with XL2/XLH4, growth assays in defined media with LPC as sole fatty acid source, and subcellular localization in P. falciparum","pmids":["41043577"],"confidence":"Medium","gaps":["Individual catalytic contribution of PARE to LPC hydrolysis not quantified","Relationship between LPC hydrolysis and prodrug activation not resolved","Membrane topology not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown how a single peripheral esterase reconciles its minor endogenous LPC-hydrolysis role with its capacity to activate structurally diverse prodrugs, and what structural features govern substrate selection.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the active site","Full endogenous substrate spectrum undefined","Mechanistic link between metabolic and prodrug-activating activities unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["XL2","XLH4"],"other_free_text":["Mutations in PARE confer in vitro resistance to pepstatin esters and MMV011438 by loss of prodrug-activating de-esterification [#0].","Mutations in PARE confer >250-fold resistance to chlorajaponilide C, a lindenane sesquiterpenoid dimer [#1].","PARE is expressed throughout the intraerythrocytic cycle, highly conserved across strains, and non-essential; locus disruption causes negligible fitness defect [#3].","PARE is redundant with XL2 and XLH4 for scavenging choline and fatty acids from lysophosphatidylcholine; triple loss blocks replication when LPC is the sole fatty acid source [#4]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28106035","id":"PMC_28106035","title":"Esterase mutation is a mechanism of resistance to antimalarial compounds.","date":"2017","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/28106035","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31772212","id":"PMC_31772212","title":"Functional annotation of serine hydrolases in the asexual erythrocytic stage of Plasmodium falciparum.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31772212","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32970404","id":"PMC_32970404","title":"Resistance to Some But Not Other Dimeric Lindenane Sesquiterpenoid Esters Is Mediated by Mutations in a Plasmodium falciparum Esterase.","date":"2020","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32970404","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36189342","id":"PMC_36189342","title":"Efficient generation of mNeonGreen Plasmodium falciparum reporter lines enables quantitative fitness analysis.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/36189342","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PARE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41043577","id":"PMC_41043577","title":"Defining the minimal enzymatic requirements for fatty acid scavenging from lysophosphatidylcholine by erythrocytic Plasmodium falciparum.","date":"2025","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/41043577","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PARE"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5120,"output_tokens":1509,"usd":0.018998,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6519,"output_tokens":2625,"usd":0.04911,"stage2_stop_reason":"end_turn"},"total_usd":0.068108,"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\": 2017,\n      \"finding\": \"PARE (PF3D7_0709700) is a functional esterase capable of hydrolyzing pepstatin esters and de-esterifying the open-source antimalarial MMV011438 in vitro, thereby activating these prodrugs; mutations in PARE confer resistance to pepstatin esters and MMV011438 in P. falciparum.\",\n      \"method\": \"In vitro resistance selection with whole-genome sequencing of resistant mutants; recombinant PARE enzymatic assay with pepstatin esters and MMV011438 as substrates\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — recombinant enzyme activity demonstrated in vitro plus orthogonal resistance genetics (mutant selection + sequencing), multiple substrates tested, single rigorous study\",\n      \"pmids\": [\"28106035\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Mutations in PARE (PF3D7_0709700) mediate in vitro resistance to the lindenane sesquiterpenoid dimer chlorajaponilide C (>250-fold EC50 increase), indicating that PARE-mediated esterase activity is required for the potency of this compound class, though not all related sesquiterpenoid dimers depend on PARE.\",\n      \"method\": \"In vitro resistance selection, whole-genome sequencing of resistant clones, structure-resistance relationship analysis across compound series\",\n      \"journal\": \"ACS infectious diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — resistance genetics (selection + WGS) with SAR analysis across multiple compounds, single lab\",\n      \"pmids\": [\"32970404\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PARE (PF3D7_0709700) is detected as an active serine hydrolase in the asexual erythrocytic stage of P. falciparum using a fluorophosphonate-based affinity capture probe coupled to mass spectrometry, confirming active-site serine hydrolase activity in the native parasite.\",\n      \"method\": \"Fluorophosphonate-based activity-based protein profiling (ABPP) with mass spectrometry\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — chemoproteomic ABPP directly demonstrates active serine hydrolase activity in situ, but single lab and single method for this specific protein\",\n      \"pmids\": [\"31772212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The PARE (PF3D7_0709700) locus is expressed throughout the intraerythrocytic cycle, is not essential for parasite viability, and is highly conserved across P. falciparum strains, as demonstrated by successful disruption of the locus by CRISPR-based mNeonGreen reporter insertion with negligible fitness defect.\",\n      \"method\": \"CRISPR-based gene disruption/tagging, competitive growth assay (fitness measurement), fluorescence reporter expression monitoring\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct functional genetic experiment (locus disruption with fitness readout), single lab, single method\",\n      \"pmids\": [\"36189342\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PARE (PF3D7_0709700) is a membrane-associated enzyme with a substantial presence at the parasite periphery and contributes to lysophosphatidylcholine (LPC) hydrolysis; loss of PARE alone did not affect fatty acid scavenging from LPC, but when combined with loss of XL2 and XLH4 (triple knockdown), the parasites were impaired in scavenging both choline and fatty acids from LPC and could not complete a replication cycle when LPC was the sole exogenous fatty acid source.\",\n      \"method\": \"Genetic knockdown (PARE alone and in combination with XL2/XLH4), growth assays in defined media with LPC as sole fatty acid source, subcellular localization by direct imaging/fractionation\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis via triple loss-of-function with specific metabolic readout, direct membrane/peripheral localization established, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"41043577\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PARE (PF3D7_0709700) is a membrane-associated serine hydrolase/esterase expressed throughout the P. falciparum intraerythrocytic cycle that localizes to the parasite periphery, where it hydrolyzes ester bonds in lysophosphatidylcholine as a minor contributor to fatty acid scavenging alongside XL2 and XLH4, and can also activate esterified prodrugs (pepstatin esters, MMV011438, chlorajaponilide C) by de-esterification, such that mutations in PARE confer resistance to these compounds while disruption of the locus alone causes negligible fitness defect.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PARE (PF3D7_0709700) is a membrane-associated serine hydrolase expressed throughout the P. falciparum intraerythrocytic cycle whose native de-esterification activity is co-opted both for lipid metabolism and for antimalarial prodrug activation [#0, #4]. It behaves as a bona fide active-site serine hydrolase in the asexual blood stage, where it is captured by fluorophosphonate activity-based probes in situ [#2], and it hydrolyzes ester bonds in a range of substrates in vitro, activating the esterified prodrugs pepstatin esters and MMV011438 through de-esterification [#0]. Because compound potency depends on this activation step, loss-of-function mutations in PARE confer resistance to pepstatin esters and MMV011438 [#0] and to the lindenane sesquiterpenoid dimer chlorajaponilide C [#1]. Biologically, PARE localizes to the parasite periphery and contributes to hydrolysis of lysophosphatidylcholine (LPC); it is a minor, redundant player in this process, since its disruption alone causes negligible fitness defect and does not impair fatty acid scavenging, whereas combined loss of PARE with XL2 and XLH4 blocks scavenging of choline and fatty acids from LPC and prevents replication when LPC is the sole exogenous fatty acid source [#3, #4]. Beyond these roles in LPC hydrolysis and prodrug activation, no further mechanistic detail for PARE has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing that a parasite esterase can activate esterified antimalarials answered how certain prodrugs become active and revealed a genetic route to resistance.\",\n      \"evidence\": \"In vitro resistance selection with whole-genome sequencing plus recombinant enzyme assays on pepstatin esters and MMV011438 in P. falciparum\",\n      \"pmids\": [\"28106035\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Native physiological substrate not defined at this stage\", \"Structural basis of ester recognition not resolved\", \"Subcellular location not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrating that PARE is labeled by a serine-hydrolase active-site probe in intact parasites confirmed that the enzyme is catalytically active in its native context, not just as a recombinant protein.\",\n      \"evidence\": \"Fluorophosphonate-based activity-based protein profiling with mass spectrometry in asexual erythrocytic-stage P. falciparum\",\n      \"pmids\": [\"31772212\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method and single lab for this protein\", \"Does not identify endogenous substrate\", \"Activity not quantified against specific lipids\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extending resistance genetics to a structurally distinct compound class showed the prodrug-activation role generalizes, while SAR indicated the dependence is compound-specific.\",\n      \"evidence\": \"In vitro resistance selection, whole-genome sequencing, and structure-resistance analysis across chlorajaponilide-related sesquiterpenoid dimers in P. falciparum\",\n      \"pmids\": [\"32970404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct enzymatic de-esterification of chlorajaponilide C not shown in vitro\", \"Basis for which dimers require PARE not molecularly defined\", \"Single lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Genetic disruption clarified that PARE is dispensable for parasite viability, framing its endogenous role as non-essential and redundant.\",\n      \"evidence\": \"CRISPR-based mNeonGreen reporter insertion/disruption with competitive fitness assay and expression profiling in P. falciparum Dd2\",\n      \"pmids\": [\"36189342\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous function not identified by disruption alone\", \"Redundant partners not tested here\", \"Single method\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Combining localization and epistasis assigned PARE a concrete but redundant physiological role in lysophosphatidylcholine hydrolysis at the parasite periphery.\",\n      \"evidence\": \"Single and combinatorial knockdown of PARE with XL2/XLH4, growth assays in defined media with LPC as sole fatty acid source, and subcellular localization in P. falciparum\",\n      \"pmids\": [\"41043577\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Individual catalytic contribution of PARE to LPC hydrolysis not quantified\", \"Relationship between LPC hydrolysis and prodrug activation not resolved\", \"Membrane topology not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how a single peripheral esterase reconciles its minor endogenous LPC-hydrolysis role with its capacity to activate structurally diverse prodrugs, and what structural features govern substrate selection.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the active site\", \"Full endogenous substrate spectrum undefined\", \"Mechanistic link between metabolic and prodrug-activating activities unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0052689\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"GO:0017171\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0004622\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0071944\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046471\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0006629\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"XL2\", \"XLH4\"],\n    \"other_free_text\": [\n      \"Mutations in PARE confer in vitro resistance to pepstatin esters and MMV011438 by loss of prodrug-activating de-esterification [#0].\",\n      \"Mutations in PARE confer >250-fold resistance to chlorajaponilide C, a lindenane sesquiterpenoid dimer [#1].\",\n      \"PARE is expressed throughout the intraerythrocytic cycle, highly conserved across strains, and non-essential; locus disruption causes negligible fitness defect [#3].\",\n      \"PARE is redundant with XL2 and XLH4 for scavenging choline and fatty acids from lysophosphatidylcholine; triple loss blocks replication when LPC is the sole fatty acid source [#4].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0709700","name":null,"product":"prodrug activation and resistance esterase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1220300","name":null,"product":"prodrug activation and resistance esterase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0108400","name":null,"product":"prodrug activation and resistance esterase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PARE","evaluation":null}