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A genome-scale metabolic (GSM) model was developed with integrated metabolomics and constraint-based, experimental flux-balance data to predict genes essential for\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      growth as drug targets. We selected the highly ranked\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      UMP-CMP kinase (UCK) to test its necessity and the ability to inhibit parasite growth in the presence of inhibitors. Conditional deletion mutants using the DiCre recombinase system, generated by CRISPR-Cas genome editing, exhibited defective asexual growth and stage-specific developmental arrest. Based on\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      screening, inhibitors were identified that are selective for\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      UCK and exhibit antiparasitic activity. This study, for the first time, shows assertions from a GSM model identifying novel, validated \u201cdruggable\u201d targets. These findings show a role for GSM models in antimalarial drug discovery and identify\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      UCK as a novel, valid malaria drug target.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00459-25","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:33:24Z","timestamp":1758900804000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Validated antimalarial drug target discovery using genome-scale metabolic modeling"],"prefix":"10.1128","volume":"69","author":[{"given":"Supannee","family":"Taweechai","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mrxd33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biology, Molecular & Cell Biology, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Isidore Garcia","family":"Tota\u00f1es","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mrxd33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biology, Molecular & Cell Biology, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Westhead","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mrxd33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biology, Molecular & Cell Biology, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Herrera-Arozamena","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mrxd33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Foster","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mrxd33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-794X","authenticated-orcid":true,"given":"Glenn A.","family":"McConkey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mrxd33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biology, Molecular & Cell Biology, University of Leeds","place":["Leeds, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(24)00016-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0900231"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2020.11.006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06018-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504679102"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap7847"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm060687j"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/187152610791163336"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq7347"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq6241"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/9783527694082.ch21"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005895"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-4-120"},{"key":"e_1_3_2_16_2","unstructured":"Forth T. 2012. 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