Heidler S A, Radding J A
Department of Infectious Disease Research, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46285, USA.
Antimicrob Agents Chemother. 1995 Dec;39(12):2765-9. doi: 10.1128/AAC.39.12.2765.
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.
金担子素A(LY295337)是一种环缩肽类抗真菌剂,对念珠菌属具有活性。LY295337的作用机制尚不清楚。LY295337对酿酒酵母也有活性。本文报道了一株对LY295337耐药的酿酒酵母突变体的产生。发现耐药性存在于一个单基因的显性突变中,该基因被命名为AUR1(金担子素耐药)。对该基因进行了克隆和测序。在GenBank中搜索同源序列并通过BLAST分析,虽然发现该基因与酿酒酵母基因组测序项目中的一个开放阅读框以及其他几个相邻位点存在序列同源性,但仍未阐明该基因的功能。在二倍体酿酒酵母菌株中完成了aur1基因的缺失。随后对aur1/aur1Δ二倍体进行孢子形成和分离,结果显示四分体中活孢子和非活孢子呈2:2分离,这表明aur1基因的缺失是致死性的。由于LY295337具有杀菌作用且aur1基因的缺失是致死性的,因此aur1是LY295337作用靶点的一个潜在候选基因。