THE AUR1 GENE IN SACCHAROMYCES-CEREVISIAE ENCODES DOMINANT RESISTANCETO THE ANTIFUNGAL AGENT AUREOBASIDIN-A (LY295337)

Aureobasidin A (LY295337) is a cyclic depsipeptide antifungal agent wi th activity against Candida spp, The mechanism of action of LY295337 r emains unknown, LY295337 also shows activity against the yeast Sacchar omyces cerevisiae, Generation of a mutant of S, cerevisiae resistant t o LY295337 is reported. Resistance was found to reside in a dominant m utation of a single gene,which has been named AUR1 (for aureobasidin r esistance), This gene was cloned and sequenced, A search for homologou s sequences in GenBank and by BLAST did not elucidate the function of this gene, although sequence homology to an open reading frame from th e Saccharomyces genome sequencing project and several other adjacent l oci was noted, Deletion of aur1 was accomplished in a diploid S, cerev isiae strain, Subsequent sporulation and dissection of the aur1/aur1 D elta diploid resulted in tetrads demonstrating 2:2 segregation of viab le and nonviable spores, indicating that deletion of aur1 Is lethal. A s LY295337 is fungicidal and deletion of aur1 is lethal, aur1 represen ts a potential candidate for the target of LY295337.