Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae
Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.273.18.11062
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发表时间：
1998-05-01
影响因子：
4.8
通讯作者：
Takemoto, JY
中科院分区：
文献类型：
--
作者：
Grilley, MM;Stock, SD;Takemoto, JY
酿酒酵母基因SYR 2是环脂缩酚肽庆大霉素E生长抑制所必需的，显示其是鞘脂生物合成中长链碱基的4-羟基化所必需的，提供了对该结论的四条支持线：（a）预测的Syr 2 p显示与参与烃底物的氧依赖性修饰的二铁结合膜酶的序列相似性，（B）携带破坏的SYR 2等位基因的酵母菌株产生缺乏野生型菌株中存在的4-羟基的鞘氨醇长链碱基，（c）在由SYR 2过表达菌株制备的微粒体中4-羟化酶活性增加，和（d）当在外源性4-氨基葡萄糖苷酶抑制剂存在的条件下生长时，将羟基鞘氨醇长链碱基掺入鞘脂中。E102菌株产生野生型水平的鞘脂、显著水平的羟基化极长链脂肪酸和正常酵母鞘脂头部基团的完全补充。这些结果表明，SYR 2基因是鞘脂长链碱基的4-羟基化反应所必需的，这种羟基化对生长不是必需的，并且鞘脂的4-羟基基团对于瑞幸霉素E对酵母的作用是必需的。
The Saccharomyces cerevisiae gene SYR2, necessary for growth inhibition by the cyclic lipodepsipeptide syringomycin E, is shown to be required for 4-hydroxylation of long chain bases in sphingolipid biosynthesis, Four Lines of support for this conclusion are presented: (a) the predicted Syr2p shows sequence similarity to diiron-binding membrane enzymes involved in oxygen-dependent modifications of hydrocarbon substrates, (b) yeast strains carrying a disrupted SYR2 allele produced sphingoid long chain bases lacking the 4-hydroxyl group present in wild type strains, (c) 4-hydroxylase activity was increased in microsomes prepared from a SYR2 overexpression strain, and (d) the syringomycin E resistance phenotype of a syr2 mutant strain was suppressed when grown under conditions in which exogenous 4-hydroxysphingoid long chain bases were incorporated into sphingolipids, The syr2 strain produced wild type levels of sphingolipids, substantial levels of hydroxylated very long chain fatty acids, and the full complement of normal yeast sphingolipid head groups. These results show that the SYR2 gene is required for the 4-hydroxylation reaction of sphingolipid long chain bases, that this hydroxylation is not essential for growth, and that the 4-hydroxyl group of sphingolipids is necessary for syringomycin E action on yeast.