{"gene":"PF3D7_0303700","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2014,"finding":"The BCKDH complex (including its E2 lipoamide acyltransferase subunit, PF3D7_0303700) functionally replaces mitochondrial pyruvate dehydrogenase in Plasmodium berghei, catalysing the conversion of pyruvate to acetyl-CoA for the TCA cycle; deletion of the E1a subunit (which partners with E2) restricted parasite development to reticulocytes and completely prevented oocyst maturation during mosquito transmission.","method":"Genetic deletion of BCKDH E1a subunit in P. berghei with metabolic and phenotypic readouts (intracellular growth, virulence, oocyst development); metabolite profiling","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with defined phenotypic readouts in P. berghei; BCKDH-E2 inferred as complex member rather than directly manipulated","pmids":["25032958"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"finding":"BCKDH-E2 (PF3D7_0303700), the E2 lipoamide acyltransferase subunit of the branched-chain keto acid dehydrogenase complex, localises to the mitochondrion of P. falciparum, as shown by direct fluorescence imaging.","method":"Subcellular localisation by fluorescence microscopy (live imaging/fractionation) demonstrating mitochondrial localisation of the E2 subunit of BCDH","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localisation experiment in single study, single lab","pmids":["25116855"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"BCKDH-E2 (PF3D7_0303700) is lipoylated in the mitochondrion through a novel two-component mechanism requiring both LipL1 and LipL2; LipL1 alone cannot lipoylate BCKDH-E2, and LipL2 alone has no ligase activity, but together they achieve lipoylation exclusively under strong reducing conditions—distinct from the H-protein lipoylation pathway.","method":"In vitro lipoylation assay with purified LipL1 and LipL2 under defined redox conditions; western blot detection of lipoylated E2 subunit","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution assay with defined enzymatic components, redox manipulation, and multiple orthogonal readouts in a single rigorous study","pmids":["25116855"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"BCKDH-E2 (PF3D7_0303700) and the α-ketoglutarate dehydrogenase E2 subunit (KDH) are in a synthetic lethal relationship in P. falciparum: simultaneous disruption of both mitochondrial ketoacid dehydrogenase enzymes is lethal, whereas single deletions are tolerated, demonstrating that together they are essential for mitochondrial acetyl-CoA production. Lipoylation by LipL2 is required for BCKDH activity and hence for parasite survival via acetyl-CoA metabolism.","method":"Metabolite-labelling experiments with genetic deletions affecting mitochondrial dehydrogenase activity; synthetic lethality analysis; isotope tracing of acetyl-CoA metabolism","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis (synthetic lethality) combined with metabolite labelling in P. falciparum; multiple orthogonal methods in a single rigorous study","pmids":["37068227"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Mitochondrial acetyl-CoA produced by BCKDH (including BCKDH-E2, PF3D7_0303700) and KDH is required for histone acetylation and protein acetylation outside the mitochondrion in P. falciparum, demonstrating that mitochondrial acetyl-CoA metabolism feeds nuclear/cytosolic acetylation reactions essential for parasite survival.","method":"Metabolite-labelling and genetic deletion experiments; measurement of histone and protein acetylation levels in dehydrogenase-disrupted parasite lines","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, genetic KO with protein acetylation readout; BCKDH-E2 contribution inferred as part of the complex rather than directly manipulated alone","pmids":["37068227"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"BCKDH-E2 (PF3D7_0303700) is a lipoamide acyltransferase subunit of the mitochondrial branched-chain keto acid dehydrogenase complex in Plasmodium; it localises to the parasite mitochondrion, is lipoylated there through a novel redox-sensitive two-enzyme mechanism (LipL1 + LipL2), and functions together with KDH in a synthetically lethal relationship to produce acetyl-CoA that feeds both the TCA cycle and extra-mitochondrial protein acetylation essential for parasite survival and transmission."},"narrative":{"mechanistic_narrative":"BCKDH-E2 (PF3D7_0303700) is the E2 lipoamide acyltransferase subunit of the mitochondrial branched-chain keto acid dehydrogenase (BCKDH) complex in Plasmodium, where the complex functions in the parasite as the enzyme that generates acetyl-CoA for central carbon metabolism [PMID:25032958, PMID:37068227]. In P. berghei, BCKDH substitutes for the missing mitochondrial pyruvate dehydrogenase by converting pyruvate to acetyl-CoA feeding the TCA cycle, and this activity is required for blood-stage development and for oocyst maturation during mosquito transmission [PMID:25032958]. The E2 subunit itself localises to the P. falciparum mitochondrion [PMID:25116855] and is activated by lipoylation through a distinctive two-component mechanism: neither LipL1 nor LipL2 alone can modify BCKDH-E2, but together they lipoylate it exclusively under strongly reducing conditions, a redox-gated route distinct from the H-protein lipoylation pathway [PMID:25116855]. Functionally, BCKDH-E2 and the α-ketoglutarate dehydrogenase E2 subunit (KDH) are synthetically lethal in P. falciparum—single deletions are tolerated but simultaneous loss is not—establishing that the two ketoacid dehydrogenases together supply the mitochondrial acetyl-CoA pool required for survival, with LipL2-dependent lipoylation being necessary for BCKDH activity [PMID:37068227]. This mitochondrial acetyl-CoA in turn is required for histone and other protein acetylation outside the mitochondrion, linking BCKDH-E2 metabolism to nuclear/cytosolic acetylation essential for the parasite [PMID:37068227]. Beyond its role as a lipoylated E2 subunit of this complex, no further mechanistic detail specific to PF3D7_0303700 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing that in Plasmodium the BCKDH complex, of which BCKDH-E2 is the acyltransferase subunit, performs the pyruvate-to-acetyl-CoA reaction normally assigned to pyruvate dehydrogenase, and that this is required for transmission.","evidence":"Genetic deletion of the BCKDH E1a subunit (partner of E2) in P. berghei with growth, virulence, oocyst, and metabolite readouts","pmids":["25032958"],"confidence":"Medium","gaps":["BCKDH-E2 was inferred as a complex member, not directly manipulated","Does not resolve the specific catalytic contribution of the E2 subunit versus other subunits","Shown in P. berghei; not tested in P. falciparum here"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2014,"claim":"Determining where the E2 subunit acts and how it is post-translationally activated resolved that BCKDH-E2 is mitochondrial and is lipoylated by a novel redox-gated two-enzyme mechanism.","evidence":"Fluorescence localisation and in vitro lipoylation reconstitution with purified LipL1 and LipL2 under defined redox conditions in P. falciparum","pmids":["25116855"],"confidence":"High","gaps":["Structural basis of LipL1/LipL2 cooperativity not defined","Physiological redox trigger for lipoylation in vivo not established","Localisation shown in a single study/lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Testing whether the two mitochondrial ketoacid dehydrogenases are individually essential revealed a synthetic lethal relationship, defining BCKDH-E2 together with KDH as the source of an essential mitochondrial acetyl-CoA pool.","evidence":"Genetic epistasis (synthetic lethality) with isotope tracing of acetyl-CoA metabolism in P. falciparum","pmids":["37068227"],"confidence":"High","gaps":["Does not isolate the BCKDH-E2 contribution independently of the full complex","Quantitative partition of acetyl-CoA flux between BCKDH and KDH not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Linking mitochondrial output to gene regulation showed that acetyl-CoA generated by BCKDH/KDH is required for extra-mitochondrial histone and protein acetylation, connecting central metabolism to epigenetic regulation.","evidence":"Metabolite labelling and genetic deletion with measurement of histone/protein acetylation in dehydrogenase-disrupted P. falciparum lines","pmids":["37068227"],"confidence":"Medium","gaps":["BCKDH-E2 contribution inferred as part of the complex, not directly manipulated alone","Mechanism of acetyl-CoA export from mitochondrion not defined","Which acetylation targets are functionally decisive not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How BCKDH-E2 (PF3D7_0303700) functions in isolation—its individual catalytic activity, structure, and any role separate from KDH-dependent acetyl-CoA supply—remains uncharacterized.","evidence":"No discovery in the corpus manipulates or reconstitutes BCKDH-E2 activity independently of the complex","pmids":[],"confidence":"Low","gaps":["No structure of BCKDH-E2 in the corpus","No direct measurement of its acyltransferase activity alone","Regulation of its expression or turnover unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex"],"partners":["BCKDH E1A SUBUNIT","LIPL1 (LIPOYLATION ENZYME)","LIPL2 (LIPOYLATION ENZYME)","ALPHA-KETOGLUTARATE DEHYDROGENASE E2 SUBUNIT (KDH) — SYNTHETIC LETHAL PARTNER"],"other_free_text":["Lipoylated exclusively under strongly reducing conditions via a two-component LipL1+LipL2 mechanism distinct from the H-protein pathway [#2]","In P. berghei, BCKDH functionally replaces mitochondrial pyruvate dehydrogenase and is required for oocyst maturation during mosquito transmission [#0]","Synthetically lethal with KDH in P. falciparum; together they supply an essential mitochondrial acetyl-CoA pool [#3]","Mitochondrial acetyl-CoA from BCKDH/KDH feeds extra-mitochondrial histone and protein acetylation [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25032958","id":"PMC_25032958","title":"BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei.","date":"2014","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/25032958","citation_count":102,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":false},{"pmid":"25116855","id":"PMC_25116855","title":"Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum.","date":"2014","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25116855","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37068227","id":"PMC_37068227","title":"The mitochondrion of Plasmodium falciparum is required for cellular acetyl-CoA metabolism and protein acetylation.","date":"2023","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/37068227","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4208,"output_tokens":1669,"usd":0.018829,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6707,"output_tokens":2778,"usd":0.051492,"stage2_stop_reason":"end_turn"},"total_usd":0.070321,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"The BCKDH complex (including its E2 lipoamide acyltransferase subunit, PF3D7_0303700) functionally replaces mitochondrial pyruvate dehydrogenase in Plasmodium berghei, catalysing the conversion of pyruvate to acetyl-CoA for the TCA cycle; deletion of the E1a subunit (which partners with E2) restricted parasite development to reticulocytes and completely prevented oocyst maturation during mosquito transmission.\",\n      \"method\": \"Genetic deletion of BCKDH E1a subunit in P. berghei with metabolic and phenotypic readouts (intracellular growth, virulence, oocyst development); metabolite profiling\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with defined phenotypic readouts in P. berghei; BCKDH-E2 inferred as complex member rather than directly manipulated\",\n      \"pmids\": [\"25032958\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"BCKDH-E2 (PF3D7_0303700), the E2 lipoamide acyltransferase subunit of the branched-chain keto acid dehydrogenase complex, localises to the mitochondrion of P. falciparum, as shown by direct fluorescence imaging.\",\n      \"method\": \"Subcellular localisation by fluorescence microscopy (live imaging/fractionation) demonstrating mitochondrial localisation of the E2 subunit of BCDH\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localisation experiment in single study, single lab\",\n      \"pmids\": [\"25116855\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"BCKDH-E2 (PF3D7_0303700) is lipoylated in the mitochondrion through a novel two-component mechanism requiring both LipL1 and LipL2; LipL1 alone cannot lipoylate BCKDH-E2, and LipL2 alone has no ligase activity, but together they achieve lipoylation exclusively under strong reducing conditions—distinct from the H-protein lipoylation pathway.\",\n      \"method\": \"In vitro lipoylation assay with purified LipL1 and LipL2 under defined redox conditions; western blot detection of lipoylated E2 subunit\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution assay with defined enzymatic components, redox manipulation, and multiple orthogonal readouts in a single rigorous study\",\n      \"pmids\": [\"25116855\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"BCKDH-E2 (PF3D7_0303700) and the α-ketoglutarate dehydrogenase E2 subunit (KDH) are in a synthetic lethal relationship in P. falciparum: simultaneous disruption of both mitochondrial ketoacid dehydrogenase enzymes is lethal, whereas single deletions are tolerated, demonstrating that together they are essential for mitochondrial acetyl-CoA production. Lipoylation by LipL2 is required for BCKDH activity and hence for parasite survival via acetyl-CoA metabolism.\",\n      \"method\": \"Metabolite-labelling experiments with genetic deletions affecting mitochondrial dehydrogenase activity; synthetic lethality analysis; isotope tracing of acetyl-CoA metabolism\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis (synthetic lethality) combined with metabolite labelling in P. falciparum; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"37068227\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Mitochondrial acetyl-CoA produced by BCKDH (including BCKDH-E2, PF3D7_0303700) and KDH is required for histone acetylation and protein acetylation outside the mitochondrion in P. falciparum, demonstrating that mitochondrial acetyl-CoA metabolism feeds nuclear/cytosolic acetylation reactions essential for parasite survival.\",\n      \"method\": \"Metabolite-labelling and genetic deletion experiments; measurement of histone and protein acetylation levels in dehydrogenase-disrupted parasite lines\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, genetic KO with protein acetylation readout; BCKDH-E2 contribution inferred as part of the complex rather than directly manipulated alone\",\n      \"pmids\": [\"37068227\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"BCKDH-E2 (PF3D7_0303700) is a lipoamide acyltransferase subunit of the mitochondrial branched-chain keto acid dehydrogenase complex in Plasmodium; it localises to the parasite mitochondrion, is lipoylated there through a novel redox-sensitive two-enzyme mechanism (LipL1 + LipL2), and functions together with KDH in a synthetically lethal relationship to produce acetyl-CoA that feeds both the TCA cycle and extra-mitochondrial protein acetylation essential for parasite survival and transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BCKDH-E2 (PF3D7_0303700) is the E2 lipoamide acyltransferase subunit of the mitochondrial branched-chain keto acid dehydrogenase (BCKDH) complex in Plasmodium, where the complex functions in the parasite as the enzyme that generates acetyl-CoA for central carbon metabolism [#0, #3]. In P. berghei, BCKDH substitutes for the missing mitochondrial pyruvate dehydrogenase by converting pyruvate to acetyl-CoA feeding the TCA cycle, and this activity is required for blood-stage development and for oocyst maturation during mosquito transmission [#0]. The E2 subunit itself localises to the P. falciparum mitochondrion [#1] and is activated by lipoylation through a distinctive two-component mechanism: neither LipL1 nor LipL2 alone can modify BCKDH-E2, but together they lipoylate it exclusively under strongly reducing conditions, a redox-gated route distinct from the H-protein lipoylation pathway [#2]. Functionally, BCKDH-E2 and the α-ketoglutarate dehydrogenase E2 subunit (KDH) are synthetically lethal in P. falciparum—single deletions are tolerated but simultaneous loss is not—establishing that the two ketoacid dehydrogenases together supply the mitochondrial acetyl-CoA pool required for survival, with LipL2-dependent lipoylation being necessary for BCKDH activity [#3]. This mitochondrial acetyl-CoA in turn is required for histone and other protein acetylation outside the mitochondrion, linking BCKDH-E2 metabolism to nuclear/cytosolic acetylation essential for the parasite [#4]. Beyond its role as a lipoylated E2 subunit of this complex, no further mechanistic detail specific to PF3D7_0303700 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that in Plasmodium the BCKDH complex, of which BCKDH-E2 is the acyltransferase subunit, performs the pyruvate-to-acetyl-CoA reaction normally assigned to pyruvate dehydrogenase, and that this is required for transmission.\",\n      \"evidence\": \"Genetic deletion of the BCKDH E1a subunit (partner of E2) in P. berghei with growth, virulence, oocyst, and metabolite readouts\",\n      \"pmids\": [\"25032958\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"BCKDH-E2 was inferred as a complex member, not directly manipulated\", \"Does not resolve the specific catalytic contribution of the E2 subunit versus other subunits\", \"Shown in P. berghei; not tested in P. falciparum here\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Determining where the E2 subunit acts and how it is post-translationally activated resolved that BCKDH-E2 is mitochondrial and is lipoylated by a novel redox-gated two-enzyme mechanism.\",\n      \"evidence\": \"Fluorescence localisation and in vitro lipoylation reconstitution with purified LipL1 and LipL2 under defined redox conditions in P. falciparum\",\n      \"pmids\": [\"25116855\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of LipL1/LipL2 cooperativity not defined\", \"Physiological redox trigger for lipoylation in vivo not established\", \"Localisation shown in a single study/lab\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Testing whether the two mitochondrial ketoacid dehydrogenases are individually essential revealed a synthetic lethal relationship, defining BCKDH-E2 together with KDH as the source of an essential mitochondrial acetyl-CoA pool.\",\n      \"evidence\": \"Genetic epistasis (synthetic lethality) with isotope tracing of acetyl-CoA metabolism in P. falciparum\",\n      \"pmids\": [\"37068227\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not isolate the BCKDH-E2 contribution independently of the full complex\", \"Quantitative partition of acetyl-CoA flux between BCKDH and KDH not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Linking mitochondrial output to gene regulation showed that acetyl-CoA generated by BCKDH/KDH is required for extra-mitochondrial histone and protein acetylation, connecting central metabolism to epigenetic regulation.\",\n      \"evidence\": \"Metabolite labelling and genetic deletion with measurement of histone/protein acetylation in dehydrogenase-disrupted P. falciparum lines\",\n      \"pmids\": [\"37068227\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"BCKDH-E2 contribution inferred as part of the complex, not directly manipulated alone\", \"Mechanism of acetyl-CoA export from mitochondrion not defined\", \"Which acetylation targets are functionally decisive not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How BCKDH-E2 (PF3D7_0303700) functions in isolation—its individual catalytic activity, structure, and any role separate from KDH-dependent acetyl-CoA supply—remains uncharacterized.\",\n      \"evidence\": \"No discovery in the corpus manipulates or reconstitutes BCKDH-E2 activity independently of the complex\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structure of BCKDH-E2 in the corpus\", \"No direct measurement of its acyltransferase activity alone\", \"Regulation of its expression or turnover unknown\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0043754\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0009107\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006086\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0006099\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006475\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex\"\n    ],\n    \"partners\": [\n      \"BCKDH E1a subunit\",\n      \"LipL1 (lipoylation enzyme)\",\n      \"LipL2 (lipoylation enzyme)\",\n      \"alpha-ketoglutarate dehydrogenase E2 subunit (KDH) — synthetic lethal partner\"\n    ],\n    \"other_free_text\": [\n      \"Lipoylated exclusively under strongly reducing conditions via a two-component LipL1+LipL2 mechanism distinct from the H-protein pathway [#2]\",\n      \"In P. berghei, BCKDH functionally replaces mitochondrial pyruvate dehydrogenase and is required for oocyst maturation during mosquito transmission [#0]\",\n      \"Synthetically lethal with KDH in P. falciparum; together they supply an essential mitochondrial acetyl-CoA pool [#3]\",\n      \"Mitochondrial acetyl-CoA from BCKDH/KDH feeds extra-mitochondrial histone and protein acetylation [#4]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0303700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 3 cited papers name other catalogue genes (PF3D7_0923600, PF3D7_0820700, PF3D7_1314600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0303700","name":null,"product":"lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0402300","name":null,"product":"lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0839400","name":null,"product":"lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"BCKDH-E2","evaluation":null}