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Identification of the Enzymes Mediating the Maturation of the Seryl‐tRNA Synthetase Inhibitor SB‐217452 during the Biosynthesis of Albomycins
Author(s) -
Ushimaru Richiro,
Chen Zhang,
Zhao Houyuan,
Fan Pohsun,
Liu Hungwen
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915275
Subject(s) - adenylylation , biosynthesis , chemistry , serine , nonribosomal peptide , enzyme , biochemistry , dipeptide , stereochemistry , moiety , dehydratase , amino acid
Albomycin δ 2 is a sulfur‐containing sideromycin natural product that shows potent antibacterial activity against clinically important pathogens. The l ‐serine‐thioheptose dipeptide partial structure, known as SB‐217452, has been found to be the active seryl‐tRNA synthetase inhibitor component of albomycin δ 2 . Herein, it is demonstrated that AbmF catalyzes condensation between the 6′‐amino‐4′‐thionucleoside with the d ‐ ribo configuration and seryl‐adenylate supplied by the serine adenylation activity of AbmK. Formation of the dipeptide is followed by C3′‐epimerization to produce SB‐217452 with the d ‐ xylo configuration, which is catalyzed by the radical S ‐adenosyl‐ l ‐methionine enzyme AbmJ. Gene deletion suggests that AbmC is involved in peptide assembly linking SB‐217452 with the siderophore moiety. This study establishes how the albomycin biosynthetic machinery generates its antimicrobial component SB‐217452.