1887

Abstract

Acetolactate synthase catalyses the first common step in isoleucine and valine biosynthesis and is the target of several classes of inhibitors. The gene, encoding acetolactate synthase, was identified by complementation of a mutant. is highly resistant to the commercially available acetolactate synthase inhibitor, sulfometuron methyl (SM). Expression of in conferred SM resistance, indicating that the SM resistance of is due, at least in part, to Ilv2p. The gene was disrupted. The mutants were auxotrophic for isoleucine and valine and the auxotrophy was satisfied by these amino acids only when proline, and not ammonium, was the nitrogen source, indicating nitrogen regulation of amino acid transport. mutants rapidly lost viability at 37 °C and when starved for isoleucine and valine. Consistent with these phenotypes, an mutant was avirulent and unable to survive in mice. Because Ilv2p is required for virulence and survival , inhibitors of branched-chain amino acid biosynthesis may make valuable antifungal agents.

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2004-05-01
2019-10-16
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