A critical role of mevalonate for peptidoglycan synthesis in Staphylococcus aureus.
A critical role of mevalonate for peptidoglycan synthesis in Staphylococcus aureus.
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DOI：
10.1038/srep22894
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发表时间：
2016-03-10
影响因子：
4.6
通讯作者：
Sekimizu K
中科院分区：
文献类型：
--
作者：
Matsumoto Y;Yasukawa J;Ishii M;Hayashi Y;Miyazaki S;Sekimizu K
3-羟基-3-甲基-戊二酰-CoA（HMG-CoA）还原酶是一种甲羟戊酸合成酶，是金黄色葡萄球菌生长所必需的。然而，这种酶在细胞生长中的重要作用仍然不清楚。在这里，我们表明，三个突变体具有单碱基取代的mvaA基因，编码HMG-CoA还原酶，表现出温度敏感的表型。通过添加甲羟戊酸或法呢基二磷酸（由甲羟戊酸合成的产物）抑制表型。法呢基二磷酸是十一异戊二烯基磷酸的前体，其是肽聚糖合成所需的。在非允许条件下，mvaA突变体的肽聚糖合成速率降低，并且通过加入甲羟戊酸抑制表型。温度敏感突变体中突变MvaA蛋白的HMG-CoA还原酶活性低于野生型MvaA蛋白。我们的遗传和生化分析结果表明，HMG-CoA还原酶产生的甲羟戊酸是S.金黄色葡萄球菌细胞生长。
3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, a mevalonate synthetase, is required for the growth of Staphylococcus aureus. However, the essential role of the enzyme in cell growth has remained unclear. Here we show that three mutants possessed single-base substitutions in the mvaA gene, which encodes HMG-CoA reductase, show a temperature-sensitive phenotype. The phenotype was suppressed by the addition of mevalonate or farnesyl diphosphate, which is a product synthesized from mevalonate. Farnesyl diphosphate is a precursor of undecaprenyl phosphate that is required for peptidoglycan synthesis. The rate of peptidoglycan synthesis was decreased in the mvaA mutants under the non-permissive conditions and the phenotype was suppressed by the addition of mevalonate. HMG-CoA reductase activities of mutant MvaA proteins in the temperature sensitive mutants were lower than that of wild-type MvaA protein. Our findings from genetic and biochemical analyses suggest that mevalonate produced by HMG-CoA reductase is required for peptidoglycan synthesis for S. aureus cell growth.