{"gene":"PF3D7_1312000","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2003,"finding":"Recombinant MCAT (PF3D7_1312000) catalyzes the transfer of a malonyl group from malonyl-CoA to pfACP in vitro, establishing its enzymatic function as malonyl-CoA:ACP transacylase in P. falciparum type II fatty acid biosynthesis.","method":"In vitro biochemical assay with purified recombinant pfMCAT and pfACP","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro enzymatic reconstitution with purified recombinant protein, single lab but clear functional demonstration","pmids":["12549938"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"pfACP(trans), the construct of pfACP containing an amino-terminal apicoplast transit peptide, is NOT a substrate for MCAT (PF3D7_1312000), indicating that the transit peptide interferes with malonyl transfer.","method":"In vitro enzymatic assay comparing pfACP and pfACP(trans) as substrates for recombinant pfMCAT","journal":"Biochemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro negative result with purified recombinant proteins, single lab, single method","pmids":["12549938"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"The product of the MCAT reaction, malonyl-pfACP, is a substrate for pfKASIII, placing MCAT upstream of pfKASIII in the type II fatty acid synthesis initiation pathway.","method":"Sequential in vitro enzymatic assay: malonyl-pfACP generated by pfMCAT was used as substrate for pfKASIII","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct biochemical pathway reconstitution linking MCAT product to downstream enzyme, single lab with clear functional demonstration","pmids":["12549938"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Genetic disruption of MCAT (PF3D7_1312000 ortholog) in rodent malaria parasites does not affect asexual blood-stage propagation or mosquito-stage development, but MCAT KO sporozoites fail to initiate blood-stage infection in mice, with hepatic parasites showing impaired nuclear division and apicoplast biogenesis, leading to a defect in hepatic merozoite formation and late liver-stage attenuation.","method":"Genetic knockout (MCAT KO) in rodent malaria parasites with phenotypic analysis of blood-stage, mosquito-stage, and liver-stage development; apicoplast biogenesis and nuclear division assessed in hepatic stages","journal":"NPJ vaccines","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with defined cellular phenotypes across multiple life-cycle stages, single lab, multiple orthogonal readouts (apicoplast biogenesis, nuclear division, merozoite formation)","pmids":["40379677"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"MCAT (PF3D7_1312000) is a malonyl-CoA:ACP transacylase that catalyzes the transfer of malonyl groups from malonyl-CoA to the acyl carrier protein (pfACP) as the initiating step of apicoplast type II fatty acid synthesis; the malonyl-pfACP product feeds directly into pfKASIII-catalyzed condensation reactions, and genetic disruption of MCAT in rodent malaria reveals that it is essential specifically for late liver-stage development—including apicoplast biogenesis and nuclear division in hepatic parasites—but dispensable for asexual blood-stage and mosquito-stage propagation."},"narrative":{"mechanistic_narrative":"MCAT (PF3D7_1312000) is the malonyl-CoA:ACP transacylase that initiates apicoplast type II fatty acid biosynthesis in malaria parasites [PMID:12549938]. Recombinant P. falciparum MCAT transfers a malonyl group from malonyl-CoA to the acyl carrier protein pfACP in vitro, and the resulting malonyl-pfACP is a direct substrate for pfKASIII, placing MCAT immediately upstream of the KASIII-catalyzed condensation step in the pathway [PMID:12549938]. Substrate recognition depends on the mature form of pfACP: pfACP bearing its N-terminal apicoplast transit peptide is not accepted, indicating the transit peptide interferes with malonyl transfer [PMID:12549938]. Genetic disruption in the rodent malaria parasite P. berghei defines MCAT's physiological role as stage-specific—it is dispensable for asexual blood-stage and mosquito-stage propagation but essential for late liver-stage development, where MCAT-null hepatic parasites show impaired apicoplast biogenesis and nuclear division and fail to form hepatic merozoites [PMID:40379677]. Beyond this catalytic and life-cycle characterization, no structural or regulatory detail for MCAT has been established in the available corpus.","teleology":[{"year":2003,"claim":"Establishing whether PF3D7_1312000 was a functional malonyl-CoA:ACP transacylase settled the identity of the enzyme initiating parasite type II fatty acid synthesis.","evidence":"In vitro biochemical assay with purified recombinant pfMCAT and pfACP","pmids":["12549938"],"confidence":"High","gaps":["Catalytic residues and structural basis of malonyl transfer not defined","Kinetic parameters and regulation not characterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"claim":"Testing transit-peptide-bearing pfACP versus mature pfACP addressed which form of the carrier protein MCAT recognizes, revealing that the apicoplast transit peptide blocks catalysis.","evidence":"In vitro enzymatic assay comparing pfACP and pfACP(trans) as MCAT substrates","pmids":["12549938"],"confidence":"Medium","gaps":["Single in vitro negative result","Structural basis of the transit-peptide interference not resolved","Physiological relevance of the unprocessed form unclear"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"claim":"Feeding the malonyl-pfACP product into a pfKASIII reaction placed MCAT within the ordered initiation pathway, linking its output to downstream condensation.","evidence":"Sequential in vitro enzymatic assay: MCAT-generated malonyl-pfACP used as substrate for pfKASIII","pmids":["12549938"],"confidence":"High","gaps":["In vitro reconstitution only; in vivo flux through this route not measured","Full downstream elongation cascade not tested in the same system"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Genetic knockout across the life cycle answered where MCAT is physiologically required, demonstrating a specific essential role in late liver-stage development rather than in blood or mosquito stages.","evidence":"MCAT knockout in rodent malaria parasites with phenotypic analysis of apicoplast biogenesis, nuclear division, and merozoite formation across life-cycle stages","pmids":["40379677"],"confidence":"Medium","gaps":["Single lab; not confirmed in P. falciparum","Mechanistic link between loss of fatty acid synthesis and the apicoplast/nuclear-division defect not resolved","Whether the defect is due solely to loss of transacylase activity not tested by catalytic-dead complementation"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How MCAT activity is regulated and how its loss mechanistically couples to apicoplast biogenesis and nuclear division in hepatic parasites remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of MCAT","No catalytic-dead rescue linking enzymatic activity to the liver-stage phenotype","P. falciparum knockout phenotype not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFACP (ACYL CARRIER PROTEIN) — MALONYL ACCEPTOR SUBSTRATE","PFKASIII — ACCEPTS THE MALONYL-PFACP PRODUCT DOWNSTREAM"],"other_free_text":["MCAT-generated malonyl-pfACP is the direct substrate for pfKASIII, placing MCAT at the initiation step of apicoplast type II fatty acid synthesis [#2].","In P. berghei, MCAT is dispensable for blood- and mosquito-stage development but essential for late liver-stage progression, with knockout hepatic parasites showing defective apicoplast biogenesis and nuclear division [#3].","The apicoplast transit peptide on pfACP prevents it from serving as an MCAT substrate in vitro [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12549938","id":"PMC_12549938","title":"The initiating steps of a type II fatty acid synthase in Plasmodium falciparum are catalyzed by pfACP, pfMCAT, and pfKASIII.","date":"2003","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12549938","citation_count":75,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MCAT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27477098","id":"PMC_27477098","title":"Deorphanization of Malonyl CoA:ACP Transacylase Drug Target in Plasmodium falciparum (PfFabD) Using Bacterial Antagonists: A 'Piggyback' Approach for Antimalarial Drug Discovery.","date":"2012","source":"Molecular informatics","url":"https://pubmed.ncbi.nlm.nih.gov/27477098","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26535573","id":"PMC_26535573","title":"Multivariate PLS Modeling of Apicomplexan FabD-Ligand Interaction Space for Mapping Target-Specific Chemical Space and Pharmacophore Fingerprints.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26535573","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40379677","id":"PMC_40379677","title":"A Plasmodium LARC GAP provides preerythrocytic, stage and species transcending protection in mice.","date":"2025","source":"NPJ vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/40379677","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MCAT","malonyl CoA-acyl carrier protein transacylase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4998,"output_tokens":1168,"usd":0.016257,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6061,"output_tokens":2184,"usd":0.042452,"stage2_stop_reason":"end_turn"},"total_usd":0.058709,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"Recombinant MCAT (PF3D7_1312000) catalyzes the transfer of a malonyl group from malonyl-CoA to pfACP in vitro, establishing its enzymatic function as malonyl-CoA:ACP transacylase in P. falciparum type II fatty acid biosynthesis.\",\n      \"method\": \"In vitro biochemical assay with purified recombinant pfMCAT and pfACP\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro enzymatic reconstitution with purified recombinant protein, single lab but clear functional demonstration\",\n      \"pmids\": [\"12549938\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"pfACP(trans), the construct of pfACP containing an amino-terminal apicoplast transit peptide, is NOT a substrate for MCAT (PF3D7_1312000), indicating that the transit peptide interferes with malonyl transfer.\",\n      \"method\": \"In vitro enzymatic assay comparing pfACP and pfACP(trans) as substrates for recombinant pfMCAT\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro negative result with purified recombinant proteins, single lab, single method\",\n      \"pmids\": [\"12549938\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"The product of the MCAT reaction, malonyl-pfACP, is a substrate for pfKASIII, placing MCAT upstream of pfKASIII in the type II fatty acid synthesis initiation pathway.\",\n      \"method\": \"Sequential in vitro enzymatic assay: malonyl-pfACP generated by pfMCAT was used as substrate for pfKASIII\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct biochemical pathway reconstitution linking MCAT product to downstream enzyme, single lab with clear functional demonstration\",\n      \"pmids\": [\"12549938\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Genetic disruption of MCAT (PF3D7_1312000 ortholog) in rodent malaria parasites does not affect asexual blood-stage propagation or mosquito-stage development, but MCAT KO sporozoites fail to initiate blood-stage infection in mice, with hepatic parasites showing impaired nuclear division and apicoplast biogenesis, leading to a defect in hepatic merozoite formation and late liver-stage attenuation.\",\n      \"method\": \"Genetic knockout (MCAT KO) in rodent malaria parasites with phenotypic analysis of blood-stage, mosquito-stage, and liver-stage development; apicoplast biogenesis and nuclear division assessed in hepatic stages\",\n      \"journal\": \"NPJ vaccines\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with defined cellular phenotypes across multiple life-cycle stages, single lab, multiple orthogonal readouts (apicoplast biogenesis, nuclear division, merozoite formation)\",\n      \"pmids\": [\"40379677\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"MCAT (PF3D7_1312000) is a malonyl-CoA:ACP transacylase that catalyzes the transfer of malonyl groups from malonyl-CoA to the acyl carrier protein (pfACP) as the initiating step of apicoplast type II fatty acid synthesis; the malonyl-pfACP product feeds directly into pfKASIII-catalyzed condensation reactions, and genetic disruption of MCAT in rodent malaria reveals that it is essential specifically for late liver-stage development—including apicoplast biogenesis and nuclear division in hepatic parasites—but dispensable for asexual blood-stage and mosquito-stage propagation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MCAT (PF3D7_1312000) is the malonyl-CoA:ACP transacylase that initiates apicoplast type II fatty acid biosynthesis in malaria parasites [#0]. Recombinant P. falciparum MCAT transfers a malonyl group from malonyl-CoA to the acyl carrier protein pfACP in vitro, and the resulting malonyl-pfACP is a direct substrate for pfKASIII, placing MCAT immediately upstream of the KASIII-catalyzed condensation step in the pathway [#0, #2]. Substrate recognition depends on the mature form of pfACP: pfACP bearing its N-terminal apicoplast transit peptide is not accepted, indicating the transit peptide interferes with malonyl transfer [#1]. Genetic disruption in the rodent malaria parasite P. berghei defines MCAT's physiological role as stage-specific—it is dispensable for asexual blood-stage and mosquito-stage propagation but essential for late liver-stage development, where MCAT-null hepatic parasites show impaired apicoplast biogenesis and nuclear division and fail to form hepatic merozoites [#3]. Beyond this catalytic and life-cycle characterization, no structural or regulatory detail for MCAT has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing whether PF3D7_1312000 was a functional malonyl-CoA:ACP transacylase settled the identity of the enzyme initiating parasite type II fatty acid synthesis.\",\n      \"evidence\": \"In vitro biochemical assay with purified recombinant pfMCAT and pfACP\",\n      \"pmids\": [\"12549938\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Catalytic residues and structural basis of malonyl transfer not defined\", \"Kinetic parameters and regulation not characterized\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Testing transit-peptide-bearing pfACP versus mature pfACP addressed which form of the carrier protein MCAT recognizes, revealing that the apicoplast transit peptide blocks catalysis.\",\n      \"evidence\": \"In vitro enzymatic assay comparing pfACP and pfACP(trans) as MCAT substrates\",\n      \"pmids\": [\"12549938\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single in vitro negative result\", \"Structural basis of the transit-peptide interference not resolved\", \"Physiological relevance of the unprocessed form unclear\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Feeding the malonyl-pfACP product into a pfKASIII reaction placed MCAT within the ordered initiation pathway, linking its output to downstream condensation.\",\n      \"evidence\": \"Sequential in vitro enzymatic assay: MCAT-generated malonyl-pfACP used as substrate for pfKASIII\",\n      \"pmids\": [\"12549938\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vitro reconstitution only; in vivo flux through this route not measured\", \"Full downstream elongation cascade not tested in the same system\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Genetic knockout across the life cycle answered where MCAT is physiologically required, demonstrating a specific essential role in late liver-stage development rather than in blood or mosquito stages.\",\n      \"evidence\": \"MCAT knockout in rodent malaria parasites with phenotypic analysis of apicoplast biogenesis, nuclear division, and merozoite formation across life-cycle stages\",\n      \"pmids\": [\"40379677\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; not confirmed in P. falciparum\", \"Mechanistic link between loss of fatty acid synthesis and the apicoplast/nuclear-division defect not resolved\", \"Whether the defect is due solely to loss of transacylase activity not tested by catalytic-dead complementation\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MCAT activity is regulated and how its loss mechanistically couples to apicoplast biogenesis and nuclear division in hepatic parasites remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of MCAT\", \"No catalytic-dead rescue linking enzymatic activity to the liver-stage phenotype\", \"P. falciparum knockout phenotype not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004314\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006633\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"pfACP (acyl carrier protein) — malonyl acceptor substrate\", \"pfKASIII — accepts the malonyl-pfACP product downstream\"],\n    \"other_free_text\": [\n      \"MCAT-generated malonyl-pfACP is the direct substrate for pfKASIII, placing MCAT at the initiation step of apicoplast type II fatty acid synthesis [#2].\",\n      \"In P. berghei, MCAT is dispensable for blood- and mosquito-stage development but essential for late liver-stage progression, with knockout hepatic parasites showing defective apicoplast biogenesis and nuclear division [#3].\",\n      \"The apicoplast transit peptide on pfACP prevents it from serving as an MCAT substrate in vitro [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1312000","name":null,"product":"malonyl CoA-acyl carrier protein transacylase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1410500","name":null,"product":"malonyl CoA-acyl carrier protein transacylase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1412700","name":null,"product":"malonyl CoA-acyl carrier protein transacylase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MCAT","evaluation":null}