ISSN:
1617-4623
Keywords:
Key words Aureobasidin A
;
Drug-resistant mutant
;
Target protein
;
Microtubule
;
Yeast
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
Notes:
Abstract Aureobasidin A (AbA), a cyclic depsipeptide produced by Aureobasidium pullulans R106, is highly toxic to fungi including Saccharomyces cerevisiae. We isolated several dominant mutants of S. cerevisiae which are resistant to more than 25 μg/ml of AbA. From a genomic library of one such AUR1 mutant, the AUR1 R (for aureobasidin resistant) mutant gene was isolated as a gene that confers resistance to AbA on wild-type cells. Its nucleotide sequence showed that the predicted polypeptide is a hydrophobic protein composed of 401 amino acids, which contains several possible transmembrane domains and at least one predicted N-linked glycosylation site. Comparison of the mutant gene with the wild-type aur1 + gene revealed that the substitution of Phe at position 158 by Tyr is responsible for acquisition of AbA resistance. We suggest that the gene product of the wild-type aur1 + is a target for AbA on the basis of following results. Firstly, cells that overexpress the wild-type aur1 + gene become resistant to AbA, just as cells with an AUR1 R mutation do. Secondly, disruption of the aur1 + gene demonstrated that it is essential for growth. Thirdly, in the cells with a disrupted aur1 locus, pleiotropic morphological changes including disappearance of microtubules, degradation of tubulin and abnormal deposition of chitin were observed. Some of these abnormalities are also observed when wild-type cells are treated with AbA. The abnormality in microtubules suggests that the Aur1 protein is involved in microtubule organization and stabilization.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02172923
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