Staphylococcus aureus produces staphyloxanthin, a C30 carotenoid with golden color, as an antioxidant to promote bacterial resistance to reactive oxygen species. The biosynthesis pathway of staphyloxanthin involves a series of catalytic enzymes. Aldehyde dehydrogenase (AldH) is a dehydrogenase recently identified to convert 4,4’-diaponeurosporenaldehyde into 4,4’-diaponeurosporenoic acid during staphyloxanthin biosynthesis. Here, we present the crystallographic structures of apo- and holo-forms of S. aureus AldH. The dimeric enzyme contains a unique C-terminal helix, which resembles a “gatekeeper” helix found in human membrane-bound fatty aldehyde dehydrogenase (FALDH). Particularly, the helix adopts “open” and “closed” conformations in apo- and holo-AldH, respectively, to control the access of the substrate tunnel. Mutagenesis in combination with in vitro and in vivo activity assays identifies several residues essential for S. aureus AldH substrate recognition and enzyme catalytic turnover. Our results provide insights into substrate recognition of S. aureus AldH toward polyunsaturated long-chain aldehydes at atomic resolution.

中文翻译：

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金黄色葡萄球菌醛脱氢酶对底物门控机制的结构性认识。

金黄色葡萄球菌可生产金黄色葡萄球菌素（一种金黄的C30类胡萝卜素），作为一种抗氧化剂，可增强细菌对活性氧的抵抗力。金黄色素的生物合成途径涉及一系列催化酶。醛脱氢酶（AldH）是最近鉴定出的一种脱氢酶，可在葡萄黄素生物合成过程中将4,4'-双嘧糖醛酸转化为4,4'-双嘧糖醛酸。在这里，我们介绍金黄色葡萄球菌AldH的脱辅基和全环型的晶体结构。该二聚酶包含一个独特的C末端螺旋，类似于在人膜结合脂肪醛脱氢酶（FALDH）中发现的“守门人”螺旋。特别地，螺旋线分别在载脂蛋白和全脂AldH中采用“开放”和“封闭”构型，以控制衬底隧道的进入。诱变与体外和体内活性分析相结合，鉴定出几个对金黄色葡萄球菌AldH底物识别和酶催化转换至关重要的残基。我们的结果提供了洞察到金黄色葡萄球菌AldH对多不饱和长链醛在原子分辨率下的底物识别的见识。