Publications

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

  Ghssein G., Brutesco C., Ouerdane L., Fojcik C., Izaute A., Wang S., Hajjar C., Lobinski R., Lemaire D., Richaud P., Voulhoux R., Espaillat A., Cava F., Pignol D., Borezee-Durant E., Arnoux P.

  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 ... >> More

  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. << Less

  Science 352:1105-1109(2016) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Structural basis for the broad specificity of a new family of amino-acid racemases.

  Espaillat A., Carrasco-Lopez C., Bernardo-Garcia N., Pietrosemoli N., Otero L.H., Alvarez L., de Pedro M.A., Pazos F., Davis B.M., Waldor M.K., Hermoso J.A., Cava F.

  Broad-spectrum amino-acid racemases (Bsrs) enable bacteria to generate noncanonical D-amino acids, the roles of which in microbial physiology, including the modulation of cell-wall structure and the dissolution of biofilms, are just beginning to be appreciated. Here, extensive crystallographic, mu ... >> More

  Broad-spectrum amino-acid racemases (Bsrs) enable bacteria to generate noncanonical D-amino acids, the roles of which in microbial physiology, including the modulation of cell-wall structure and the dissolution of biofilms, are just beginning to be appreciated. Here, extensive crystallographic, mutational, biochemical and bioinformatic studies were used to define the molecular features of the racemase BsrV that enable this enzyme to accommodate more diverse substrates than the related PLP-dependent alanine racemases. Conserved residues were identified that distinguish BsrV and a newly defined family of broad-spectrum racemases from alanine racemases, and these residues were found to be key mediators of the multispecificity of BrsV. Finally, the structural analysis of an additional Bsr that was identified in the bioinformatic analysis confirmed that the distinguishing features of BrsV are conserved among Bsr family members. << Less

  Acta Crystallogr. D 70:79-90(2014) [PubMed] [EuropePMC]

  This publication is cited by 12 other entries.

• Discovery, characterization, and structure of a cofactor-independent histidine racemase from the oral pathogen Fusobacterium nucleatum.

  Lamer T., Chen P., Venter M.J., van Belkum M.J., Wijewardane A., Wu C., Lemieux M.J., Vederas J.C.

  Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso ... >> More

  Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we characterize this enzyme as a histidine racemase (HisR), and found that catalytic turnover is ∼10,000× faster with L-histidine than with L,L-lanthionine. Kinetic experiments suggest that HisR functions as a cofactor-independent racemase and that turnover is specific for histidine, while crystal structures of catalytic cysteine to serine mutants (C67S or C209S) reveal this enzyme in its substrate-unbound, open conformation. Currently, the only other reported cofactor-independent histidine racemase is CntK from Staphylococcus aureus, which is used in the biosynthesis of staphylopine, a broad-spectrum metallophore that increases virulence of S. aureus. However, CntK shares only 28% sequence identity with HisR, and their genes exist in different genomic contexts. Knockout of hisR in F. nucleatum results in a small but reproducible lag in growth compared to WT during exponential phase, suggesting that HisR may play a role in growth of this periodontal pathogen. << Less

  J. Biol. Chem. 300:107896-107896(2024) [PubMed] [EuropePMC]