The myo-inositol-1-phosphate synthase gene is essential in Trypanosoma brucei.
The de novo synthesis of myo-inositol occurs via a two-step process: first, glucose 6-phosphate is converted into inositol 1-phosphate by an INO1 (myo-inositol-1-phosphate synthase; EC 5.5.1.4); then, it is dephosphorylated by an inositol monophosphatase. The myo-inositol can then be incorporated into PI (phosphatidylinositol), which is utilized in a variety of cellular functions, including the biosynthesis of GPI (glycosylphosphatidylinositol) anchors. A putative INO1 was identified in the Trypanosoma brucei genome database and, by recombinant expression in Escherichia coli, was shown to be a catalytically active INO1. To investigate the importance of INO1, we created a conditional knockout, which, under non-permissive conditions, showed that INO1 is an essential gene in bloodstream form T. brucei and that the de novo synthesized myo-inositol is used for the formation of PI and GPI anchors.
Martin
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KL
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Smith
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TK
D000818:Animals; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D017353:Gene Deletion; D017125:Genes, Protozoan; D006017:Glycolipids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D007296:Myo-Inositol-1-Phosphate Synthase / Q000235:genetics*; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics*
D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D010743:Phospholipids; C115336:glycoinositolphospholipid, Trypanosoma; D007296:Myo-Inositol-1-Phosphate Synthase