title: Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus.
abstract: Metal acquisition is a vital microbial process in metal-scarce environments, such as inside a host. Using metabolomic exploration, targeted mutagenesis, and biochemical analysis, we discovered an operon in Staphylococcus aureus that encodes the different functions required for the biosynthesis and trafficking of a broad-spectrum metallophore related to plant nicotianamine (here called staphylopine). The biosynthesis of staphylopine reveals the association of three enzyme activities: a histidine racemase, an enzyme distantly related to nicotianamine synthase, and a staphylopine dehydrogenase belonging to the DUF2338 family. Staphylopine is involved in nickel, cobalt, zinc, copper, and iron acquisition, depending on the growth conditions. This biosynthetic pathway is conserved across other pathogens, thus underscoring the importance of this metal acquisition strategy in infection.
authors.affiliation: Laboratoire de Bioénergétique Cellulaire, Institut de Biosciences et Biotechnology Aix-Marseille (BIAM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 13108 Saint-Paul-lès-Durance, France. UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Ghssein
authors.affiliation: Laboratoire de Bioénergétique Cellulaire, Institut de Biosciences et Biotechnology Aix-Marseille (BIAM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 13108 Saint-Paul-lès-Durance, France. UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Brutesco
authors.affiliation: Université de Pau et des Pays de l'Adour/CNRS, Laboratoire de Chimie Analytique Bio-inorganique et Environnement, IPREM-UMR5254, Hélioparc, 2, Avenue Angot, 64053 Pau, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Ouerdane
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Fojcik
authors.affiliation: Laboratoire de Bioénergétique Cellulaire, Institut de Biosciences et Biotechnology Aix-Marseille (BIAM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 13108 Saint-Paul-lès-Durance, France. UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Izaute
authors.affiliation: Université de Pau et des Pays de l'Adour/CNRS, Laboratoire de Chimie Analytique Bio-inorganique et Environnement, IPREM-UMR5254, Hélioparc, 2, Avenue Angot, 64053 Pau, France.
authors.forename: Shuanglong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratoire de Bioénergétique Cellulaire, Institut de Biosciences et Biotechnology Aix-Marseille (BIAM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 13108 Saint-Paul-lès-Durance, France. UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Hajjar
authors.affiliation: Université de Pau et des Pays de l'Adour/CNRS, Laboratoire de Chimie Analytique Bio-inorganique et Environnement, IPREM-UMR5254, Hélioparc, 2, Avenue Angot, 64053 Pau, France.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Lobinski
authors.affiliation: UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France. Lab Interact Protein Metal, BIAM, CEA, 13108 Saint-Paul-lès-Durance, France.
authors.forename: David
authors.initials: D
authors.lastname: Lemaire
authors.affiliation: UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France. Lab Bioenerget Biotechnol Bacteries et Microalgues, BIAM, CEA, 13108 Saint-Paul-lès-Durance, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Richaud
authors.affiliation: CNRS et Aix-Marseille Université, Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Marseille, France.
authors.forename: Romé
authors.initials: R
authors.lastname: Voulhoux
authors.affiliation: Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden.
authors.forename: Akbar
authors.initials: A
authors.lastname: Espaillat
authors.affiliation: Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden.
authors.forename: Felipe
authors.initials: F
authors.lastname: Cava
authors.affiliation: Laboratoire de Bioénergétique Cellulaire, Institut de Biosciences et Biotechnology Aix-Marseille (BIAM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 13108 Saint-Paul-lès-Durance, France. UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Pignol
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Borezée-Durant
authors.affiliation: Laboratoire de Bioénergétique Cellulaire, Institut de Biosciences et Biotechnology Aix-Marseille (BIAM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), 13108 Saint-Paul-lès-Durance, France. UMR 7265, Centre National de Recherche Scientifique, Saint-Paul-lès-Durance, France. Aix Marseille Université, Marseille, France. pascal.arnoux@cea.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Arnoux
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000591:Amino Acid Isomerases / Q000235:genetics / Q000378:metabolism*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D053898:Biosynthetic Pathways; D003035:Cobalt / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006639:Histidine / Q000737:chemistry; D007093:Imidazoles / Q000378:metabolism*; D055442:Metabolome; D009532:Nickel / Q000378:metabolism; D009876:Operon; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D015032:Zinc / Q000378:metabolism
chemical_list: D007093:Imidazoles; C000609243:staphylopine; C082893:nicotianamine; D003035:Cobalt; D006639:Histidine; D001383:Azetidinecarboxylic Acid; D003300:Copper; D009532:Nickel; D010088:Oxidoreductases; D019883:Alkyl and Aryl Transferases; C118230:nicotianamine synthase; D000591:Amino Acid Isomerases; D015032:Zinc