期刊
MBIO
卷 10, 期 4, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/mBio.01319-19
关键词
bioenergetics; facultative anaerobes; hydroxylases; iron-sulfur; oxygen; peptidase U32; proteobacteria; quinones; respiration; ubiquinone
类别
资金
- Agence Nationale de la Recherche (ANR) [ANR Blanc (An)aeroUbi ANR-15-CE11-0001-02]
- French National Research Agency (Labex program DYNAMO) [ANR-11-LABX-0011]
- Grenoble Alpes Data Institute - French National Research Agency [ANR-15-IDEX-02]
Most bacteria can generate ATP by respiratory metabolism, in which electrons are shuttled from reduced substrates to terminal electron acceptors, via quinone molecules like ubiquinone. Dioxygen (O-2) is the terminal electron acceptor of aerobic respiration and serves as a co-substrate in the biosynthesis of ubiquinone. Here, we characterize a novel, O-2-independent pathway for the biosynthesis of ubiquinone. This pathway relies on three proteins, UbiT (YhbT), UbiU (YhbU), and UbiV (YhbV). UbiT contains an SCP2 lipid-binding domain and is likely an accessory factor of the biosynthetic pathway, while UbiU and UbiV (UbiU-UbiV) are involved in hydroxylation reactions and represent a novel class of O-2-independent hydroxylases. We demonstrate that UbiU-UbiV form a heterodimer, wherein each protein binds a 4Fe-4S cluster via conserved cysteines that are essential for activity. The UbiT, -U, and -V proteins are found in alpha-, beta-, and gammaproteo-bacterial clades, including several human pathogens, supporting the widespread distribution of a previously unrecognized capacity to synthesize ubiquinone in the absence of O-2. Together, the O-2-dependent and O-2-independent ubiquinone biosynthesis pathways contribute to optimizing bacterial metabolism over the entire O-2 range. IMPORTANCE In order to colonize environments with large O-2 gradients or fluctuating O-2 levels, bacteria have developed metabolic responses that remain incompletely understood. Such adaptations have been recently linked to antibiotic resistance, virulence, and the capacity to develop in complex ecosystems like the microbiota. Here, we identify a novel pathway for the biosynthesis of ubiquinone, a molecule with a key role in cellular bioenergetics. We link three uncharacterized genes of Escherichia coli to this pathway and show that the pathway functions independently from O-2. In contrast, the long-described pathway for ubiquinone biosynthesis requires O-2 as a substrate. In fact, we find that many proteobacteria are equipped with the O-2-dependent and O-2-independent pathways, supporting that they are able to synthesize ubiquinone over the entire O-2 range. Overall, we propose that the novel O-2-independent pathway is part of the metabolic plasticity developed by proteobacteria to face various environmental O-2 levels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据