Publications

• An organic O donor for biological hydroxylation reactions.

  Ferizhendi K.K., Simon P., Pelosi L., Sechet E., Arulanandam R., Chehade M.H., Rey M., Onal D., Flandrin L., Chreim R., Faivre B., Vo S.C., Arias-Cartin R., Barras F., Fontecave M., Bouveret E., Lombard M., Pierrel F.

  All biological hydroxylation reactions are thought to derive the oxygen atom from one of three inorganic oxygen donors, O₂, H₂O_2, or H₂O. Here, we have identified the organic compound prephenate as the oxygen donor for the three hydroxylation steps of th ... >> More

  All biological hydroxylation reactions are thought to derive the oxygen atom from one of three inorganic oxygen donors, O₂, H₂O_2, or H₂O. Here, we have identified the organic compound prephenate as the oxygen donor for the three hydroxylation steps of the O₂-independent biosynthetic pathway of ubiquinone, a widely distributed lipid coenzyme. Prephenate is an intermediate in the aromatic amino acid pathway and genetic experiments showed that it is essential for ubiquinone biosynthesis in <i>Escherichia coli</i> under anaerobic conditions. Metabolic labeling experiments with ¹⁸O-shikimate, a precursor of prephenate, demonstrated the incorporation of ¹⁸O atoms into ubiquinone. The role of specific iron-sulfur enzymes belonging to the widespread U32 protein family is discussed. Prephenate-dependent hydroxylation reactions represent a unique biochemical strategy for adaptation to anaerobic environments. << Less

  Proc. Natl. Acad. Sci. U.S.A. 121:e2321242121-e2321242121(2024) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Ubiquinone biosynthesis over the entire O2 range: characterization of a conserved O2-independent pathway.

  Pelosi L., Vo C.D., Abby S.S., Loiseau L., Rascalou B., Hajj Chehade M., Faivre B., Gousse M., Chenal C., Touati N., Binet L., Cornu D., Fyfe C.D., Fontecave M., Barras F., Lombard M., Pierrel F.

  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 ... >> More

  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.<b>IMPORTANCE</b> 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 <i>Escherichia coli</i> 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. << Less

  MBio 10:E01319-E01319(2019) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.