Premium
Posttranslationally Acting Arginases Provide a Ribosomal Route to Non‐proteinogenic Ornithine Residues in Diverse Peptide Sequences
Author(s) -
Mordhorst Silja,
Morinaka Brandon I.,
Vagstad Anna L.,
Piel Jörn
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008990
Subject(s) - peptide , ornithine , biochemistry , amino acid , arginase , biology , arginine , ribosomal rna , enzyme , chemistry , gene
Ornithine is a component of many bioactive nonribosomal peptides but is challenging to incorporate into ribosomal products. We recently identified OspR, a cyanobacterial arginase‐like enzyme that installs ornithines in the antiviral ribosomally synthesised and posttranslationally modified peptide (RiPP) landornamide A. Here we report that OspR belongs to a larger family of peptide arginases from diverse organisms and RiPP types. In E. coli , seven selected enzymes converted arginine into ornithine with little preference for the leader type. A broad range of peptide sequences was modified, including polyarginine repeats. We also generated analogues of ornithine‐containing nonribosomal peptides using RiPP technology. Five pseudo‐nonribosomal products with ornithines at the correct positions were obtained, including a brevicidine analogue containing ornithine and a d ‐amino acid installed by the peptide epimerase OspD. These results suggest new opportunities for peptide bioengineering.