Staphylococcus aureus SufT: an essential iron-sulphur cluster assembly factor in cells experiencing a high-demand for lipoic acid.
Staphylococcus aureus SufT: an essential iron-sulphur cluster assembly factor in cells experiencing a high-demand for lipoic acid.
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DOI：
10.1111/mmi.13539
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发表时间：
2016-12
影响因子：
3.6
通讯作者：
Boyd JM
中科院分区：
文献类型：
--
作者：
Mashruwala AA;Roberts CA;Bhatt S;May KL;Carroll RK;Shaw LN;Boyd JM
金黄色葡萄球菌SufT仅由未知功能域59 （DUF59）组成，并在铁硫（Fe-S）蛋白的成熟中发挥作用。我们报告说，当金黄色葡萄球菌的生长严重依赖于利用脂酰胺的酶时，SufT是必不可少的，但当这种依赖减少时，SufT是必不可少的。LipA需要Fe-S簇来合成硫辛酸（LA）， ΔsufT菌株的表型表明LA产量减少，脂酰胺需要酶的活性降低。发酵生长，无clpC等位基因，或通过TCA循环的通量减少，减少了对LA的需求，并使SufT变得不必要。在ΔclpC菌株中Fe-S簇载体Nfu的丰度增加，null clpC等位基因无法抑制ΔsufT Δnfu菌株的LA需求。nfu的过表达抑制了ΔsufT菌株对LA的需求。我们提出了一个模型，其中SufT和DUF59在金黄色葡萄球菌细胞中对脂酰胺依赖性酶有很高的需求，对于holo-LipA的成熟至关重要。研究结果表明，在载脂蛋白成熟过程中，对Fe-S酶产物的需求是一个控制Fe-S簇组装因子使用的因素。细胞中含有铁硫（Fe-S）簇，利用蛋白质和促进簇组装的蛋白质。硫辛酸（LA）是铁- s簇依赖酶LipA的产物。SufT Fe-S簇组装因子在对脂酰胺依赖性酶有高需求的细胞中是必不可少的。我们认为对Fe-S酶产物的需求是控制载脂蛋白成熟过程中Fe-S组装因子使用的一个因素。
S. aureus SufT is composed solely of the domain of unknown function 59 (DUF59) and has a role in the maturation of iron-sulfur (Fe-S) proteins. We report that SufT is essential for S. aureus when growth is heavily reliant upon lipoamide-utilizing enzymes, but dispensable when this reliance is decreased. LipA requires Fe-S clusters for lipoic acid (LA) synthesis and a ΔsufT strain had phenotypes suggestive of decreased LA production and decreased activities of lipoamide-requiring enzymes. Fermentative growth, a null clpC allele, or decreased flux through the TCA cycle diminished the demand for LA and rendered SufT non-essential. Abundance of the Fe-S cluster carrier Nfu was increased in a ΔclpC strain and a null clpC allele was unable to suppress the LA requirement of a ΔsufT Δnfu strain. Over-expression of nfu suppressed the LA requirement of the ΔsufT strain. We propose a model wherein SufT, and by extension the DUF59, is essential for the maturation of holo-LipA in S. aureus cells experiencing a high demand for lipoamide-dependent enzymes. The findings presented suggest that the demand for products of Fe-S enzymes is a factor governing the usage of one Fe-S cluster assembly factor over another in the maturation of apo-proteins. Cells contain iron-sulfur (Fe-S) cluster utilizing proteins and proteins that facilitate cluster assembly. Lipoic acid (LA) is a product of the Fe-S cluster dependent enzyme LipA. The SufT Fe-S cluster assembly factor is essential in cells experiencing a high demand for lipoamide-dependent enzymes. We propose that the demand for products of Fe-S enzymes is a factor governing the usage of one Fe-S assembly factor over another in the maturation of apo-proteins.
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