An Unexpected Split-Merge Pathway in the Assembly of the Symmetric Nonribosomal Peptide Antibiotic Closthioamide.
Angew Chem Int Ed Engl
; 60(8): 4104-4109, 2021 02 19.
Article
em En
| MEDLINE
| ID: mdl-33119936
ABSTRACT
Closthioamide (CTA) is a symmetric nonribosomal peptide (NRP) comprised of two diaminopropane-linked polythioamidated monomers. CTA is biosynthesized by Ruminiclostridium cellulolyticum via an atypical NRP synthetase (NRPS)-independent biosynthetic pathway. Although the logic for monomer assembly was recently elucidated, the strategy for the biosynthesis and incorporation of the diamine linker remained a mystery. By means of genome editing, synthesis, and inâ
vitro biochemical assays, we demonstrate that the final steps in CTA maturation proceed through a surprising split-merge pathway involving the dual use of a thiotemplated intermediate. This pathway includes the first examples of an aldo-keto reductase catalyzing the reductive release of a thiotemplated product, and of a transthioamidating transglutaminase. In addition to clarifying the remaining steps in CTA assembly, our data shed light on largely unexplored pathways for NRPS-independent peptide biosynthesis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tioamidas
/
Antibacterianos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article