1887

Abstract

We identified and attempted to disrupt the homoserine and/or threonine biosynthetic genes encoding aspartate kinase (), homoserine kinase () and threonine synthase (); however, each gene proved recalcitrant to disruption. By replacing the endogenous promoters of and with the copper-repressible promoter, we showed that and were essential for the growth of in rich media, when ammonium was the nitrogen source, or when threonine was supplied as an amino acid instead of a dipeptide. Moreover, the severity of the growth defect associated with or repression increased with increasing incubation temperature. We believe this to be the first demonstration of threonine biosynthetic genes being essential in a fungus. The necessity of these genes for growth, particularly at physiologically relevant temperatures, makes threonine biosynthetic genes ideal anti-cryptococcal drug targets.

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2008-09-01
2020-04-07
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