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The O2-independent pathway of ubiquinone biosynthesis is essential for denitrification in Pseudomonas aeruginosa

Chau-Duy-Tam Vo 1 Julie Michaud 2 Sylvie Elsen 3 Bruno Faivre 1 Emmanuelle Bouveret 4 Frédéric Barras 4 Marc Fontecave 1 Fabien Pierrel 2 Murielle Lombard 1, * Ludovic Pelosi 2, * 
* Corresponding author
1 Chaire Chimie des processus biologiques
LCPB - Laboratoire de Chimie des Processus Biologiques
2 TIMC-IMAG-GEM - Génomique et Évolution des Microorganismes
TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525
3 PBRC - Pathogenèse bactérienne et réponses cellulaires
CNRS - Centre National de la Recherche Scientifique : ERL 526, BCI - Biologie du Cancer et de l'Infection
Abstract : 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 recently discovered in E. coli. However, 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 hereafter 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 pathogenicity of this bacterium in individuals with cystic fibrosis, our results highlight that the O2-independent UQ biosynthetic pathway may represent a possible target for antibiotics development to manage P. aeruginosa infections.
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Chau-Duy-Tam Vo, Julie Michaud, Sylvie Elsen, Bruno Faivre, Emmanuelle Bouveret, et al.. The O2-independent pathway of ubiquinone biosynthesis is essential for denitrification in Pseudomonas aeruginosa. Journal of Biological Chemistry, 2020, 295 (27), pp.9021-9032. ⟨10.1074/jbc.RA120.013748⟩. ⟨pasteur-02746713⟩



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