{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:35:02Z","timestamp":1790876102747,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The biosynthesis of the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), cofactors used by 2% of proteins, occurs through the sequential action of two ubiquitous activities: a riboflavinkinase (RFK) that phosphorylates the riboflavin (RF) precursor to FMN, and a FMN:adenylyltransferase (FMNAT) that transforms FMN into FAD. In most mammals two different monofunctional enzymes have each of these activities, but in prokaryotes a single bifunctional enzyme, FAD synthase (FADS), holds them. Differential structural and functional traits for RFK and FMNAT catalysis between bacteria and mammals, as well as within the few bacterial FADSs so far characterized, has envisaged the potentiality of FADSs from pathogens as targets for the development of species\u2010specific inhibitors. Here, we particularly characterize the FADS from the ovine pathogen\n                    <jats:italic>Brucella ovis<\/jats:italic>\n                    (BoFADS), causative agent of brucellosis. We show that BoFADS has RFK activity independently of the media redox status, but its FMNAT activity (in both forward and reverse senses) only occurs under strong reducing conditions. Moreover, kinetics for flavin and adenine nucleotides binding to the RFK site show that BoFADS binds preferentially the substrates of the RFK reaction over the products and that the adenine nucleotide must bind prior to flavin entrapment. These results, together with multiple sequence alignments and phylogenetic analysis, point to variability in the less conserved regions as contributing to the species\u2010specific features in prokaryotic FADSs, including those from pathogens, that allow them to adopt alternative strategies in FMN and FAD biosynthesis and overall flavin homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/iub.2576","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T18:44:28Z","timestamp":1637693068000},"page":"655-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cofactors and pathogens: Flavin mononucleotide and flavin adenine dinucleotide (\n                    <scp>FAD)<\/scp>\n                    biosynthesis by the\n                    <scp>FAD<\/scp>\n                    synthase from\n                    <i>Brucella ovis<\/i>"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-2762","authenticated-orcid":false,"given":"Andrea","family":"Moreno","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias Universidad de Zaragoza  Zaragoza Spain"},{"name":"Instituto de Biocomputaci\u00f3n y F\u00edsica de Sistemas Complejos, BIFI (GBsC\u2010CSIC Joint Unit) Universidad de Zaragoza  Zaragoza Spain"},{"name":"Departamento de Biolog\u00eda, Facultad de Ciencias Universidad de Los Andes  M\u00e9rida Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9224-5854","authenticated-orcid":false,"given":"Victor","family":"Taleb","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias Universidad de Zaragoza  Zaragoza Spain"},{"name":"Instituto de Biocomputaci\u00f3n y F\u00edsica de Sistemas Complejos, BIFI (GBsC\u2010CSIC Joint Unit) Universidad de Zaragoza  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-4587","authenticated-orcid":false,"given":"Mar\u00eda","family":"Sebasti\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias Universidad de Zaragoza  Zaragoza Spain"},{"name":"Instituto de Biocomputaci\u00f3n y F\u00edsica de Sistemas Complejos, BIFI (GBsC\u2010CSIC Joint Unit) Universidad de Zaragoza  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6649-9153","authenticated-orcid":false,"given":"Ernesto","family":"Anoz\u2010Carbonell","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias Universidad de Zaragoza  Zaragoza Spain"},{"name":"Instituto de Biocomputaci\u00f3n y F\u00edsica de Sistemas Complejos, BIFI (GBsC\u2010CSIC Joint Unit) Universidad de Zaragoza  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-0046","authenticated-orcid":false,"given":"Marta","family":"Mart\u00ednez\u2010J\u00falvez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias Universidad de Zaragoza  Zaragoza Spain"},{"name":"Instituto de Biocomputaci\u00f3n y F\u00edsica de Sistemas Complejos, BIFI (GBsC\u2010CSIC Joint Unit) Universidad de Zaragoza  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0182","authenticated-orcid":false,"given":"Milagros","family":"Medina","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular, Facultad de Ciencias 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