Acyl Donor Stringency and Dehydroaminoacyl Intermediates in ß-Lactam Formation by a Non-ribosomal Peptide Synthetase.
ACS Chem Biol
; 16(5): 806-812, 2021 05 21.
Article
em En
| MEDLINE
| ID: mdl-33847484
ABSTRACT
Condensation (C) domains in non-ribosomal peptide synthetases catalyze peptide elongation steps whereby activated amino acid or peptidyl acyl donors are coupled with specific amino acid acceptors. In the biosynthesis of the ß-lactam antibiotic nocardicin A, an unusual C domain converts a seryl tetrapeptide into its pentapeptide product containing an integrated ß-lactam ring. While indirect evidence for the intermediacy of a dehydroalanyl species has been reported, here we describe observation of the elusive enzyme-bound dehydroamino acyl intermediate generated from the corresponding allo-threonyl tetrapeptide and partitioned into pentapeptide products containing either a dehydrobutyrine residue or an embedded ß-lactam. Contrary to trends in the literature where condensation domains have been deemed flexible as to acyl donor structure, this ß-lactam synthesizing domain is highly discriminating. The observation of dehydrobutyrine formation links this C domain to related clades associated with natural products containing dehydroamino acid and d-configured residues, suggesting a common mechanistic link.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Peptídeo Sintases
/
Lactamas
/
Antibacterianos
Idioma:
En
Revista:
ACS Chem Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos