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. 1995 Dec;39(12):2765–2769. doi: 10.1128/aac.39.12.2765

The AUR1 gene in Saccharomyces cerevisiae encodes dominant resistance to the antifungal agent aureobasidin A (LY295337).

S A Heidler 1, J A Radding 1
PMCID: PMC163026  PMID: 8593016

Abstract

Aureobasidin A (LY295337) is a cyclic depsipeptide antifungal agent with activity against Candida spp. The mechanism of action of LY295337 remains unknown. LY295337 also shows activity against the yeast Saccharomyces cerevisiae. Generation of a mutant of S. cerevisiae resistant to LY295337 is reported. Resistance was found to reside in a dominant mutation of a single gene which has been named AUR1 (aureobasidin resistance). This gene was cloned and sequenced. A search for homologous sequences in GenBank and by BLAST did not elucidate the function of this gene, although sequence homology too an open reading frame from the Saccharomyces genome sequencing project and several other adjacent loci was noted. Deletion of aur1 was accomplished in a diploid S. cerevisiae strain. Subsequent sporulation and dissection of the aur1/aur1 delta diploid resulted in tetrads demonstrating 2:2 segregation of viable and nonviable spores, indicating that deletion of aur1 is lethal. As LY295337 is fungicidal and deletion of aur1 is lethal, aur1 represents a potential candidate for the target of LY295337.

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Selected References

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  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Balzi E., Goffeau A. Genetics and biochemistry of yeast multidrug resistance. Biochim Biophys Acta. 1994 Aug 30;1187(2):152–162. doi: 10.1016/0005-2728(94)90102-3. [DOI] [PubMed] [Google Scholar]
  3. Balzi E., Goffeau A. Multiple or pleiotropic drug resistance in yeast. Biochim Biophys Acta. 1991 Mar 4;1073(2):241–252. doi: 10.1016/0304-4165(91)90128-4. [DOI] [PubMed] [Google Scholar]
  4. Boeke J. D., LaCroute F., Fink G. R. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. doi: 10.1007/BF00330984. [DOI] [PubMed] [Google Scholar]
  5. Boyer J., Pascolo S., Richard G. F., Dujon B. Sequence of a 7.8 kb segment on the left arm of yeast chromosome XI reveals four open reading frames, including the CAP1 gene, an intron-containing gene and a gene encoding a homolog to the mammalian UOG-1 gene. Yeast. 1993 Mar;9(3):279–287. doi: 10.1002/yea.320090307. [DOI] [PubMed] [Google Scholar]
  6. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dujon B., Alexandraki D., André B., Ansorge W., Baladron V., Ballesta J. P., Banrevi A., Bolle P. A., Bolotin-Fukuhara M., Bossier P. Complete DNA sequence of yeast chromosome XI. Nature. 1994 Jun 2;369(6479):371–378. doi: 10.1038/369371a0. [DOI] [PubMed] [Google Scholar]
  8. Haffter P., Fox T. D. Suppression of carboxy-terminal truncations of the yeast mitochondrial mRNA-specific translational activator PET122 by mutations in two new genes, MRP17 and PET127. Mol Gen Genet. 1992 Oct;235(1):64–73. doi: 10.1007/BF00286182. [DOI] [PubMed] [Google Scholar]
  9. Hoffman C. S., Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. doi: 10.1016/0378-1119(87)90131-4. [DOI] [PubMed] [Google Scholar]
  10. Ikai K., Takesako K., Shiomi K., Moriguchi M., Umeda Y., Yamamoto J., Kato I., Naganawa H. Structure of aureobasidin A. J Antibiot (Tokyo) 1991 Sep;44(9):925–933. doi: 10.7164/antibiotics.44.925. [DOI] [PubMed] [Google Scholar]
  11. Philippsen P., Stotz A., Scherf C. DNA of Saccharomyces cerevisiae. Methods Enzymol. 1991;194:169–182. doi: 10.1016/0076-6879(91)94014-4. [DOI] [PubMed] [Google Scholar]
  12. Reddy A., Maley F. Dithiothreitol improves the efficiency of yeast transformation. Anal Biochem. 1993 Jan;208(1):211–212. doi: 10.1006/abio.1993.1031. [DOI] [PubMed] [Google Scholar]
  13. Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol. 1991;194:281–301. doi: 10.1016/0076-6879(91)94022-5. [DOI] [PubMed] [Google Scholar]
  14. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sherman F., Wakem P. Mapping yeast genes. Methods Enzymol. 1991;194:38–57. doi: 10.1016/0076-6879(91)94006-x. [DOI] [PubMed] [Google Scholar]
  16. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Takesako K., Ikai K., Haruna F., Endo M., Shimanaka K., Sono E., Nakamura T., Kato I., Yamaguchi H. Aureobasidins, new antifungal antibiotics. Taxonomy, fermentation, isolation, and properties. J Antibiot (Tokyo) 1991 Sep;44(9):919–924. doi: 10.7164/antibiotics.44.919. [DOI] [PubMed] [Google Scholar]
  18. Takesako K., Kuroda H., Inoue T., Haruna F., Yoshikawa Y., Kato I., Uchida K., Hiratani T., Yamaguchi H. Biological properties of aureobasidin A, a cyclic depsipeptide antifungal antibiotic. J Antibiot (Tokyo) 1993 Sep;46(9):1414–1420. doi: 10.7164/antibiotics.46.1414. [DOI] [PubMed] [Google Scholar]

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