@article{0424955689f74fecb6a185f783e42e87,
title = "Unveiling the membrane bound dihydroorotate: Quinone oxidoreductase from Staphylococcus aureus",
abstract = "Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive organism. This protein was shown to be a FMN containing menaquinone reducing enzyme, presenting a Michaelis-Menten behaviour towards the two substrates, which was inhibited by Brequinar, Leflunomide, Lapachol, HQNO, Atovaquone and TFFA with different degrees of effectiveness. Deletion of the DHOQO coding gene (Δdhoqo) led to lower bacterial growth rates, and effected in cell morphology and metabolism, most importantly in the pyrimidine biosynthesis, here systematized for S. aureus MW2 for the first time. This work unveils the existence of a functional DHOQO in the respiratory chain of the pathogenic bacterium S. aureus, enlarging the understanding of its energy metabolism.",
keywords = "Bacterial respiration, DHODH, electron transfer, Flavoprotein, FMN, Quinone, Respiratory chain, Staphylococcus aureus",
author = "Sousa, {Filipe M.} and Patr{\'i}cia Pires and Andreia Barreto and Refojo, {Patr{\'i}cia N.} and Silva, {Micael S.} and Fernandes, {Pedro B.} and Carapeto, {Ana P.} and Robalo, {Tiago T.} and Rodrigues, {M{\'a}rio S.} and Pinho, {Mariana G.} and Cabrita, {Eurico J.} and Pereira, {Manuela M.}",
note = "Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia UI/BD/153052/2022. The work was funded by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia ( PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT , Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Funding Information: Helena Gaspar is acknowledged for the HPLC analyses and Bruno Victor for advice on modelling. F.M.S. and M.S.S. are recipients of fellowships by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (PD/BD/128213/2016 and PD/BD/128202/2016, respectively, both within the scope of the PhD program Molecular Biosciences PD/00133/2012). A.B. is recipient of a fellowship by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia UI/BD/153052/2022. The work was funded by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (PTDC/BIA-BQM/2599/2021 to M.M.P). The project was further supported by UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT, Portugal (to BioISI), by LISBOA-01-0145-FEDER-007660 cofunded by FEDER through COMPETE2020-POCI and by Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia and by UIDB/04612/2020 and UIDP/04612/2020 research unit grants from FCT (to Mostmicro). The NMR spectrometers are part of the National NMR Network (PTNMR) and are supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2023",
month = apr,
day = "1",
doi = "10.1016/j.bbabio.2022.148948",
language = "English",
volume = "1864",
journal = "Biochimica et Biophysica Acta - Bioenergetics",
issn = "0005-2728",
publisher = "Elsevier Science B.V., Inc",
number = "2",
}