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Chembiochem. 2017 Apr 4;18(7):638-646. doi: 10.1002/cbic.201600618. Epub 2017 Mar 6.

Acyl Histidines: New N-Acyl Amides from Legionella pneumophila.

Author information

1
Interdiscplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus C, Denmark.
2
Department of Microbial Pathogenesis, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
3
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT, 06511, USA.
4
Chemical Biology Institute, Yale University, 600 West Campus Drive, West Haven, CT, 06516, USA.

Abstract

Legionella pneumophila, the causative agent of Legionnaires' disease, is a Gram-negative gammaproteobacterial pathogen that infects and intracellularly replicates in human macrophages and a variety of protozoa. L. pneumophila encodes an orphan biosynthetic gene cluster (BGC) that contains isocyanide-associated biosynthetic genes and is upregulated during infection. Because isocyanide-functionalized metabolites are known to harbor invertebrate innate immunosuppressive activities in bacterial pathogen-insect interactions, we used pathway-targeted molecular networking and tetrazine-based chemoseletive ligation chemistry to characterize the metabolites from the orphan pathway in L. pneumophila. We also assessed their intracellular growth contributions in an amoeba and in murine bone-marrow-derived macrophages. Unexpectedly, two distinct groups of aromatic amino acid-derived metabolites were identified from the pathway, including a known tyrosine-derived isocyanide and a family of new N-acyl-l-histidine metabolites.

KEYWORDS:

legionellosis; metabolomics; natural product; pneumonia; secondary metabolism

PMID:
28116768
PMCID:
PMC5546091
DOI:
10.1002/cbic.201600618
[Indexed for MEDLINE]
Free PMC Article

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