期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 295, 期 27, 页码 9021-9032出版社
ELSEVIER
DOI: 10.1074/jbc.RA120.013748
关键词
ubiquinone biosynthesis; coenzyme Q; anaerobic respiration; denitrification; Pseudomonas aeruginosa; iron-sulfur protein; UbiV; UbiU; UbiT; bacterial metabolism; hydroxylation; oxygen; quinone; ubiquinone; respiratory chain; coenzyme Q10 (CoQ10); metalloprotein; anaerobic metabolism
资金
- Agence Nationale de la Recherche (ANR) [(An)aeroUbi ANR-15-CE11-0001-02, O2-taboo ANR-19-CE44-0014, DYNAMO ANR-11-LABX-0011-01, ANR-10-LABX-62-IBEID]
- University Grenoble Alpes (UGA)
- French Centre National de la Recherche Scientifique (CNRS)
- Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA)
Many proteobacteria, such asEscherichia 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 discovered recently inE. coli. Its physiological relevance is not yet understood, because MK and DMK are also present inE. coli. Here, we established that UQ(9)is the major quinone ofPseudomonas aeruginosaand is required for growth under anaerobic respiration (i.e.denitrification). We demonstrate that the ORFsPA3911,PA3912, andPA3913, which are homologs of theE. coli ubiT,ubiV, andubiUgenes, respectively, are essential for UQ(9)biosynthesis and, thus, for denitrification inP. aeruginosa. These three genes here are calledubiT(Pa),ubiV(Pa), andubiU(Pa). We show that UbiV(Pa)accommodates an iron?sulfur [4Fe-4S] cluster. Moreover, we report that UbiU(Pa)and UbiT(Pa)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 ofP. aeruginosais believed to be important for the pathogenicity of this bacterium in individuals with cystic fibrosis, our results highlight that the O-2-independent UQ biosynthetic pathway may represent a target for antibiotics development to manageP. aeruginosainfections.
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