{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:30:15Z","timestamp":1791322215331,"version":"4.3.1"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,16]],"date-time":"2014-01-16T00:00:00Z","timestamp":1389830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"Summary<\/jats:title>Intra\u2010erythrocytic stages of the malaria parasite, P<\/jats:italic><\/jats:styled-content>lasmodium falciparum<\/jats:italic>, are thought to be dependent on de novo<\/jats:italic> synthesis of phosphatidylinositol, as red blood cells (RBC<\/jats:styled-content>) lack the capacity to synthesize this phospholipid. The myo<\/jats:italic><\/jats:styled-content>\u2010inositol headgroup of PI<\/jats:styled-content> can either be synthesized de novo<\/jats:italic> or scavenged from the RBC<\/jats:styled-content>. An untargeted metabolite profiling of P<\/jats:italic><\/jats:styled-content>.\u2009falciparum<\/jats:italic> infected RBC<\/jats:styled-content> showed that trophozoite and schizont stages accumulate high levels of myo<\/jats:italic><\/jats:styled-content>\u2010inositol\u20103\u2010phosphate, indicating increased de novo <\/jats:italic>biosynthesis of myo<\/jats:italic><\/jats:styled-content>\u2010inositol from glucose 6\u2010phosphate. Metabolic labelling studies with 13<\/jats:sup>C<\/jats:roman><\/jats:styled-content>\u2010U<\/jats:styled-content>\u2010glucose in the presence and absence of exogenous inositol confirmed that de novo <\/jats:italic>myo<\/jats:italic><\/jats:styled-content>\u2010inositol synthesis occurs in parallel with myo<\/jats:italic><\/jats:styled-content>\u2010inositol salvage pathways. Unexpectedly, while both endogenous and scavenged myo<\/jats:italic><\/jats:styled-content>\u2010inositol was used to synthesize bulk PI<\/jats:styled-content>, only de novo<\/jats:italic>\u2010synthesized myo<\/jats:italic><\/jats:styled-content>\u2010inositol was incorporated into GPI<\/jats:styled-content> glycolipids. Moreover, gene disruption studies suggested that the INO1<\/jats:italic> gene, encoding myo<\/jats:italic><\/jats:styled-content>\u2010inositol 3\u2010phosphate synthase, is essential in asexual parasite stages. Together these findings suggest that P<\/jats:italic><\/jats:styled-content>.\u2009falciparum<\/jats:italic> asexual stages are critically dependent on de novo <\/jats:italic>myo<\/jats:italic><\/jats:styled-content>\u2010inositol biosynthesis for assembly of a sub\u2010pool of PI<\/jats:styled-content> species and GPI<\/jats:styled-content> biosynthesis. These findings highlight unexpected complexity in phospholipid biosynthesis in P<\/jats:italic><\/jats:styled-content>.\u2009falciparum<\/jats:italic> and a lack of redundancy in some nutrient salvage versus endogenous biosynthesis pathways.<\/jats:p>","DOI":"10.1111\/mmi.12496","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T07:12:51Z","timestamp":1387437171000},"page":"762-776","source":"Crossref","is-referenced-by-count":20,"title":["P<\/i><\/scp>lasmodium falciparum<\/i> is dependent on de novo <\/i>myo<\/i><\/scp>\u2010inositol biosynthesis for assembly of GPI<\/scp> glycolipids and infectivity"],"prefix":"10.1111","volume":"91","author":[{"given":"James I.","family":"MacRae","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Bio21 Institute of Molecular Science and Biotechnology 30 Flemington Road Melbourne Vic. 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sash","family":"Lopaticki","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity The Walter and Eliza Hall Institute of Medical Research Parkville Vic. 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Maier","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity The Walter and Eliza Hall Institute of Medical Research Parkville Vic. 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thusitha","family":"Rupasinghe","sequence":"additional","affiliation":[{"name":"Metabolomics Australia Bio21 Institute of Molecular Science and Biotechnology 30 Flemington Road Melbourne Vic. 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amsha","family":"Nahid","sequence":"additional","affiliation":[{"name":"Metabolomics Australia Bio21 Institute of Molecular Science and Biotechnology 30 Flemington Road Melbourne Vic. 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan F.","family":"Cowman","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity The Walter and Eliza Hall Institute of Medical Research Parkville Vic. 3052 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm J.","family":"McConville","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Bio21 Institute of Molecular Science and Biotechnology 30 Flemington Road Melbourne Vic. 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(82)90030-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.20347"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182009991934"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2012.09.004"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.051"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092412-155730"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301251110"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0000005"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208374200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01514-07"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwq038"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.479121"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-10-54"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(94)90054-X"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060277"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1016\/S0021-9258(17)35765-4","article-title":"Phosphatidylinositol synthase from Saccharomyces cerevisiae. 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