Discovery, Characterization, and Bioactivity of the Achromonodins: Lasso Peptides Encoded by Achromobacter.
J Nat Prod
; 86(11): 2448-2456, 2023 11 24.
Article
em En
| MEDLINE
| ID: mdl-37870195
ABSTRACT
Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of Achromobacter, a genus that contains pathogenic organisms that can infect patients with cystic fibrosis, were discovered. Using gene-refactored BGCs in E. coli, these lasso peptides, which were named achromonodin-1 and achromonodin-2, were heterologously expressed. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. The NMR structure of achromonodin-1 was determined, demonstrating that it is a threaded lasso peptide with a large loop and short tail structure, reminiscent of previously characterized lasso peptides that inhibit RNA polymerase (RNAP). Achromonodin-1 inhibits RNAP in vitro and has potent, focused activity toward Achromobacter pulmonis, another isolate from the sputum of a cystic fibrosis patient. These efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how Achromobacter isolates from certain ecological niches interact with each other.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrose Cística
/
Achromobacter
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article