Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway
ABSTRACT 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 (O2) is the terminal electron acceptor of aerobic respiration and serves as a co-substrate in the...
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American Society for Microbiology
2019
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oai:doaj.org-article:423abeece346423189b8b110c50b32a42021-11-15T16:22:10ZUbiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway10.1128/mBio.01319-192150-7511https://doaj.org/article/423abeece346423189b8b110c50b32a42019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01319-19https://doaj.org/toc/2150-7511ABSTRACT 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 (O2) is the terminal electron acceptor of aerobic respiration and serves as a co-substrate in the biosynthesis of ubiquinone. Here, we characterize a novel, O2-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 O2-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 gammaproteobacterial clades, including several human pathogens, supporting the widespread distribution of a previously unrecognized capacity to synthesize ubiquinone in the absence of O2. Together, the O2-dependent and O2-independent ubiquinone biosynthesis pathways contribute to optimizing bacterial metabolism over the entire O2 range. IMPORTANCE In order to colonize environments with large O2 gradients or fluctuating O2 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 O2. In contrast, the long-described pathway for ubiquinone biosynthesis requires O2 as a substrate. In fact, we find that many proteobacteria are equipped with the O2-dependent and O2-independent pathways, supporting that they are able to synthesize ubiquinone over the entire O2 range. Overall, we propose that the novel O2-independent pathway is part of the metabolic plasticity developed by proteobacteria to face various environmental O2 levels.Ludovic PelosiChau-Duy-Tam VoSophie Saphia AbbyLaurent LoiseauBérengère RascalouMahmoud Hajj ChehadeBruno FaivreMathieu GousséClothilde ChenalNadia TouatiLaurent BinetDavid CornuCameron David FyfeMarc FontecaveFrédéric BarrasMurielle LombardFabien PierrelAmerican Society for Microbiologyarticlebioenergeticsfacultative anaerobeshydroxylasesiron-sulfuroxygenpeptidase U32MicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
bioenergetics facultative anaerobes hydroxylases iron-sulfur oxygen peptidase U32 Microbiology QR1-502 |
| spellingShingle |
bioenergetics facultative anaerobes hydroxylases iron-sulfur oxygen peptidase U32 Microbiology QR1-502 Ludovic Pelosi Chau-Duy-Tam Vo Sophie Saphia Abby Laurent Loiseau Bérengère Rascalou Mahmoud Hajj Chehade Bruno Faivre Mathieu Goussé Clothilde Chenal Nadia Touati Laurent Binet David Cornu Cameron David Fyfe Marc Fontecave Frédéric Barras Murielle Lombard Fabien Pierrel Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway |
| description |
ABSTRACT 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 (O2) is the terminal electron acceptor of aerobic respiration and serves as a co-substrate in the biosynthesis of ubiquinone. Here, we characterize a novel, O2-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 O2-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 gammaproteobacterial clades, including several human pathogens, supporting the widespread distribution of a previously unrecognized capacity to synthesize ubiquinone in the absence of O2. Together, the O2-dependent and O2-independent ubiquinone biosynthesis pathways contribute to optimizing bacterial metabolism over the entire O2 range. IMPORTANCE In order to colonize environments with large O2 gradients or fluctuating O2 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 O2. In contrast, the long-described pathway for ubiquinone biosynthesis requires O2 as a substrate. In fact, we find that many proteobacteria are equipped with the O2-dependent and O2-independent pathways, supporting that they are able to synthesize ubiquinone over the entire O2 range. Overall, we propose that the novel O2-independent pathway is part of the metabolic plasticity developed by proteobacteria to face various environmental O2 levels. |
| format |
article |
| author |
Ludovic Pelosi Chau-Duy-Tam Vo Sophie Saphia Abby Laurent Loiseau Bérengère Rascalou Mahmoud Hajj Chehade Bruno Faivre Mathieu Goussé Clothilde Chenal Nadia Touati Laurent Binet David Cornu Cameron David Fyfe Marc Fontecave Frédéric Barras Murielle Lombard Fabien Pierrel |
| author_facet |
Ludovic Pelosi Chau-Duy-Tam Vo Sophie Saphia Abby Laurent Loiseau Bérengère Rascalou Mahmoud Hajj Chehade Bruno Faivre Mathieu Goussé Clothilde Chenal Nadia Touati Laurent Binet David Cornu Cameron David Fyfe Marc Fontecave Frédéric Barras Murielle Lombard Fabien Pierrel |
| author_sort |
Ludovic Pelosi |
| title |
Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway |
| title_short |
Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway |
| title_full |
Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway |
| title_fullStr |
Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway |
| title_full_unstemmed |
Ubiquinone Biosynthesis over the Entire O<sub>2</sub> Range: Characterization of a Conserved O<sub>2</sub>-Independent Pathway |
| title_sort |
ubiquinone biosynthesis over the entire o<sub>2</sub> range: characterization of a conserved o<sub>2</sub>-independent pathway |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/423abeece346423189b8b110c50b32a4 |
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1718426899250675712 |