Analysis of Co-localized Biosynthetic Gene Clusters Identifies a Membrane-Permeabilizing Natural Product.
J Nat Prod
; 87(7): 1694-1703, 2024 Jul 26.
Article
en En
| MEDLINE
| ID: mdl-38949271
ABSTRACT
Combination therapy is an effective strategy to combat antibiotic resistance. Multiple synergistic antimicrobial combinations are produced by enzymes encoded in biosynthetic gene clusters (BGCs) that co-localize on the bacterial genome. This phenomenon led to the hypothesis that mining co-localized BGCs will reveal new synergistic combinations of natural products. Here, we bioinformatically identified 38 pairs of co-localized BGCs, which we predict to produce natural products that are related to known compounds, including polycyclic tetramate macrolactams (PoTeMs). We further showed that ikarugamycin, a PoTeM, increases the membrane permeability of Acinetobacter baumannii and Staphylococcus aureus, which suggests that ikarugamycin might be an adjuvant that facilitates the entry of other natural products. Our work outlines a promising avenue to discover synergistic combinations of natural products by mining bacterial genomes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
/
Productos Biológicos
/
Familia de Multigenes
/
Acinetobacter baumannii
/
Antibacterianos
Idioma:
En
Revista:
J Nat Prod
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos