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Landornamides: Antiviral Ornithine‐Containing Ribosomal Peptides Discovered through Genome Mining
Author(s) -
Bösch Nina M.,
Borsa Mariana,
Greczmiel Ute,
Morinaka Brandon I.,
Gugger Muriel,
Oxenius Annette,
Vagstad Anna L.,
Piel Jörn
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201916321
Subject(s) - genome , enzyme , ribosomal rna , biochemistry , biology , gene , ornithine , lymphocytic choriomeningitis , arginase , peptide , cyanobacteria , chemistry , genetics , bacteria , arginine , amino acid , cytotoxic t cell , in vitro
Proteusins are a family of bacterial ribosomal peptides that largely remain hypothetical genome‐predicted metabolites. The only known members are the polytheonamide‐type cytotoxins, which have complex structures due to numerous unusual posttranslational modifications (PTMs). Cyanobacteria contain large numbers of putative proteusin loci. To investigate their chemical and pharmacological potential beyond polytheonamide‐type compounds, we characterized landornamide A, the product of the silent osp gene cluster from Kamptonema sp. PCC 6506. Pathway reconstruction in E. coli revealed a peptide combining lanthionines, d ‐residues, and, unusually, two ornithines introduced by the arginase‐like enzyme OspR. Landornamide A inhibited lymphocytic choriomeningitis virus infection in mouse cells, thus making it one of the few known anti‐arenaviral compounds. These data support proteusins as a rich resource of chemical scaffolds, new maturation enzymes, and bioactivities.