Unveiling the membrane bound dihydroorotate: Quinone oxidoreductase from Staphylococcus aureus.

Autor: Sousa FM; Instituto de Tecnologia Química e Biológica - António Xavier, Universidade Nova de Lisboa, Av. da República EAN, 2780-157 Oeiras, Portugal; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal., Pires P; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal., Barreto A; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal., Refojo PN; Instituto de Tecnologia Química e Biológica - António Xavier, Universidade Nova de Lisboa, Av. da República EAN, 2780-157 Oeiras, Portugal., Silva MS; UCIBIO, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal., Fernandes PB; Instituto de Tecnologia Química e Biológica - António Xavier, Universidade Nova de Lisboa, Av. da República EAN, 2780-157 Oeiras, Portugal., Carapeto AP; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal; Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal., Robalo TT; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal; Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal., Rodrigues MS; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal; Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal., Pinho MG; Instituto de Tecnologia Química e Biológica - António Xavier, Universidade Nova de Lisboa, Av. da República EAN, 2780-157 Oeiras, Portugal., Cabrita EJ; UCIBIO, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal., Pereira MM; Instituto de Tecnologia Química e Biológica - António Xavier, Universidade Nova de Lisboa, Av. da República EAN, 2780-157 Oeiras, Portugal; University of Lisbon, Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016 Lisboa, Portugal. Electronic address: mmpereira@fc.ul.pt.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Bioenergetics [Biochim Biophys Acta Bioenerg] 2023 Apr 01; Vol. 1864 (2), pp. 148948. Date of Electronic Publication: 2022 Dec 06.
DOI: 10.1016/j.bbabio.2022.148948
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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