title: Coq6 is responsible for the C4-deamination reaction in coenzyme Q biosynthesis in Saccharomyces cerevisiae.
abstract: The yeast Saccharomyces cerevisiae is able to use para-aminobenzoic acid (pABA) in addition to 4-hydroxybenzoic acid as a precursor of coenzyme Q, a redox lipid essential to the function of the mitochondrial respiratory chain. The biosynthesis of coenzyme Q from pABA requires a deamination reaction at position C4 of the benzene ring to substitute the amino group with an hydroxyl group. We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. We identify mutations in Coq6 that abrogate the C4-deamination activity, whereas preserving the C5-hydroxylation activity. Several results support that the deletion of Coq9 impacts Coq6, thus explaining the C4-deamination defect observed in Δcoq9 cells. The vast majority of flavin monooxygenases catalyze hydroxylation reactions on a single position of their substrate. Coq6 is thus a rare example of a flavin monooxygenase that is able to act on two different carbon atoms of its C4-aminated substrate, allowing its deamination and ultimately its conversion into coenzyme Q by the other proteins constituting the coenzyme Q biosynthetic pathway.
authors.affiliation: From the University of Grenoble Alpes, LCBM, UMR5249, F-38000 Grenoble, France.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ozeir
authors.affiliation: the University of Grenoble Alpes, LAPM, F-38000 Grenoble, France, the CNRS, LAPM, F-38000 Grenoble, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Pelosi
authors.affiliation: the Laboratoire de Chimie des Processus Biologiques, UMR 8229 CNRS, UPMC, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France, and the Sup'Biotech, IONIS Education Group, 66 rue Guy-Moquet, F-94800 Villejuif, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ismail
authors.affiliation: the Laboratoire de Chimie des Processus Biologiques, UMR 8229 CNRS, UPMC, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France, and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mellot-Draznieks
authors.affiliation: the Laboratoire de Chimie des Processus Biologiques, UMR 8229 CNRS, UPMC, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France, and.
authors.forename: Marc
authors.initials: M
authors.lastname: Fontecave
authors.affiliation: the University of Grenoble Alpes, LAPM, F-38000 Grenoble, France, the CNRS, LAPM, F-38000 Grenoble, France, fabien.pierrel@ujf-grenoble.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Pierrel
mesh_terms: D010129:4-Aminobenzoic Acid / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D018360:Crystallography, X-Ray; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006900:Hydroxylation; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008956:Models, Chemical; D016296:Mutagenesis; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014451:Ubiquinone / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C032165:ubiquinone 6; D014451:Ubiquinone; D002244:Carbon; D006899:Mixed Function Oxygenases; D010129:4-Aminobenzoic Acid
keywords: Saccharomyces cerevisiae; coenzyme Q; deamination; flavin; hydroxylase; isotopic tracer; mass spectrometry (MS); monooxygenase; mutagenesis