The Diiron Monooxygenase CmlA from Chloramphenicol Biosynthesis Allows Reconstitution of ß-Hydroxylation during Glycopeptide Antibiotic Biosynthesis.
ACS Chem Biol
; 14(12): 2932-2941, 2019 12 20.
Article
de En
| MEDLINE
| ID: mdl-31774267
ABSTRACT
ß-Hydroxylation plays an important role in the nonribosomal peptide biosynthesis of many important natural products, including bleomycin, chloramphenicol, and the glycopeptide antibiotics (GPAs). Various oxidative enzymes have been implicated in such a process, with the mechanism of incorporation varying from installation of hydroxyl groups in amino acid precursors prior to adenylation to direct amino acid oxidation during peptide assembly. In this work, we demonstrate the in vitro utility and scope of the unusual nonheme diiron monooxygenase CmlA from chloramphenicol biosynthesis for the ß-hydroxylation of a diverse range of carrier protein bound substrates by adapting this enzyme as a non-native trans-acting enzyme within NRPS-mediated GPA biosynthesis. The results from our study show that CmlA has a broad substrate specificity for modified phenylalanine/tyrosine residues as substrates and can be used in a practical strategy to functionally cross complement compatible NRPS biosynthesis pathways in vitro.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Glycopeptides
/
Chloramphénicol
/
Mixed function oxygenases
/
Fer
/
Antibactériens
Langue:
En
Journal:
ACS Chem Biol
Année:
2019
Type de document:
Article
Pays d'affiliation:
Australie