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Science. 2016 May 27;352(6289):1105-9. doi: 10.1126/science.aaf1018.

Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus.

Author information

1
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.
2
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.
3
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
4
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.
5
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.
6
CNRS et Aix-Marseille Université, Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Marseille, France.
7
Laboratory for Molecular Infection Medicine Sweden, Department of Molecular Biology, Umeå Centre for Microbial Research, Umeå University, Umeå, Sweden.
8
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.

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.

PMID:
27230378
DOI:
10.1126/science.aaf1018
[Indexed for MEDLINE]
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