FKS1 mutations responsible for selective resistance of Saccharomyces cerevisiae to the novel 1,3-beta-glucan synthase inhibitor arborcandin C.
Arborcandin C is a novel antibiotic with potent antifungal activity that inhibits 1,3-beta-glucan synthase in fungi. We examined spontaneous Saccharomyces cerevisiae mutants which are selectively resistant to arborcandin C and revealed that a single amino acid replacement in Fks1p of Asn(470) with Lys or of Leu(642) with Ser confers selective resistance on Fks1p mutants.
Ohyama
Takao
T
Lead Discovery Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, Japan. takaoo@shina.sankyo.co.jp
Miyakoshi
Shunichi
S
Isono
Fujio
F
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D004271:DNA, Fungal / Q000235:genetics; D025141:Drug Resistance, Fungal; D054714:Echinocandins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006020:Glycopeptides; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010455:Peptides; D010957:Plasmids / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004271:DNA, Fungal; D054714:Echinocandins; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D008565:Membrane Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C481669:arborcandin C; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase; C091618:FKS1 protein, S cerevisiae