Many proteobacteria, such as Escherichia coli, contain two main types of quinones: benzoquinones, represented by ubiquinone (UQ) and naphthoquinones, such as menaquinone (MK), and dimethyl-menaquinone (DMK). MK and DMK function predominantly in anaerobic respiratory chains, whereas UQ is the major electron carrier in the reduction of dioxygen. However, this division of labor is probably not very strict. Indeed, a pathway that produces UQ under anaerobic conditions in an UbiU-, UbiV-, and UbiT-dependent manner has been discovered recently in E. coli. Its physiological relevance is not yet understood, because MK and DMK are also present in E. coli. Here, we established that UQ9 is the major quinone of Pseudomonas aeruginosa and is required for growth under anaerobic respiration (i.e. denitrification). We demonstrate that the ORFs PA3911, PA3912, and PA3913, which are homologs of the E. coli ubiT, ubiV, and ubiU genes, respectively, are essential for UQ9 biosynthesis and, thus, for denitrification in P. aeruginosa. These three genes here are called ubiTPa, ubiVPa, and ubiUPa. We show that UbiVPa accommodates an iron–sulfur [4Fe-4S] cluster. Moreover, we report that UbiUPa and UbiTPa can bind UQ and that the isoprenoid tail of UQ is the structural determinant required for recognition by these two Ubi proteins. Since the denitrification metabolism of P. aeruginosa is believed to be important for the pathogenicity of this bacterium in individuals with cystic fibrosis, our results highlight that the O2-independent UQ biosynthetic pathway may represent a target for antibiotics development to manage P. aeruginosa infections.

中文翻译：

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不依赖 O2 的泛醌生物合成途径对于铜绿假单胞菌的反硝化作用至关重要。


许多变形菌，例如大肠杆菌，含有两种主要类型的醌：以泛醌（UQ）为代表的苯醌和萘醌，例如甲基萘醌（MK）和二甲基甲基萘醌（DMK）。 MK和DMK主要在厌氧呼吸链中发挥作用，而UQ是双氧还原中的主要电子载体。不过，这种分工恐怕不是很严格。事实上，最近在大肠杆菌中发现了一种在厌氧条件下以 UbiU、UbiV 和 UbiT 依赖性方式产生 UQ 的途径。其生理相关性尚不清楚，因为 MK 和 DMK 也存在于大肠杆菌中。在这里，我们确定 UQ9 是铜绿假单胞菌的主要醌，是无氧呼吸（即反硝化）下生长所必需的。我们证明 ORF PA3911、PA3912 和 PA3913 分别是大肠杆菌 ubiT、ubiV 和 ubiU 基因的同源物，对于 UQ9 生物合成至关重要，因此对于铜绿假单胞菌中的反硝化作用至关重要。这里这三个基因称为 ubiTPa、ubiVPa 和 ubiUPa。我们证明 UbiVPa 容纳铁硫 [4Fe-4S] 簇。此外，我们报告UbiUPa和UbiTPa可以结合UQ，并且UQ的类异戊二烯尾部是这两种Ubi蛋白识别所需的结构决定因素。由于铜绿假单胞菌的反硝化代谢被认为对该细菌在囊性纤维化个体中的致病性很重要，因此我们的结果强调，不依赖于 O2 的 UQ 生物合成途径可能代表了治疗铜绿假单胞菌感染的抗生素开发的目标。