Spermidine but not spermine is essential for hypusine biosynthesis and growth in Saccharomyces cerevisiae:: Spermine is converted to spermidine in vivo by the FMS1-amine oxidase
Spermidine but not spermine is essential for hypusine biosynthesis and growth in Saccharomyces cerevisiae:: Spermine is converted to spermidine in vivo by the FMS1-amine oxidase
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DOI：
10.1073/pnas.1835918100
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发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
Tabor, H
中科院分区：
文献类型：
--
作者：
Chattopadhyay, MK;Tabor, CW;Tabor, H
在我们早期的工作中，我们表明亚精胺或精胺可以支持spe 2Delta或spe 3Delta多胺需要突变体的生长，但尚不清楚细胞是否对这些胺有特定的需求。在目前的工作中，我们证明了亚精胺是酿酒酵母生长所必需的。我们能够通过使用spe 3Delta fms 1Delta突变体来显示这种特异性，该突变体缺乏亚精胺合酶和FMS 1编码的将精胺氧化为亚精胺的胺氧化酶。这种双突变体生长所需的多胺只能通过亚精胺来满足;即，精胺是无效的，因为在没有FMS 1基因的情况下它不能被氧化成亚精胺。我们还表明，至少有一个原因的绝对要求亚精胺的生长是其功能的特异性作为一个必要的底物羟腐胺赖氨酸修饰的eIF 5A。精胺本身不能用于羟腐胺赖氨酸修饰，除非它被Fms 1胺氧化酶氧化为亚精胺。我们已经量化了精胺在体内的转化，并表明这种转化在过表达Fms 1蛋白的菌株中显着增加。我们还表明，这种转换在酶的研究，通过使用纯化的胺氧化酶从酵母。
In our earlier work we showed that either spermidine or spermine could support the growth of spe2Delta or spe3Delta polyamine-requiring mutants, but it was unclear whether the cells had a specific requirement for either of these amines. In the current work, we demonstrate that spermidine is specifically required for the growth of Saccharomyces cerevisiae. We were able to show this specificity by using a spe3Delta fms1Delta mutant that lacked both spermidine synthase and the FMS1-encoded amine oxidase that oxidizes spermine to spermidine. The polyamine requirement for the growth of this double mutant could only be satisfied by spermidine; i.e., spermine was not effective because it cannot be oxidized to spermidine in the absence of the FMS1 gene. We also showed that at least one of the reasons for the absolute requirement for spermidine for growth is the specificity of its function as a necessary substrate for the hypusine modification of eIF5A. Spermine itself cannot be used for the hypusine modification, unless it is oxidized to spermidine by the Fms1 amine oxidase. We have quantified the conversion of spermine in vivo and have shown that this conversion is markedly increased in a strain overexpressing the Fms1 protein. We have also shown this conversion in enzymatic studies by using the purified amine oxidase from yeast.