Ribosomally synthesized thiopeptide antibiotics targeting elongation factor Tu.
J Am Chem Soc
; 131(16): 5946-55, 2009 Apr 29.
Article
en En
| MEDLINE
| ID: mdl-19338336
ABSTRACT
We identified the thiomuracins, a novel family of thiopeptides produced by a rare-actinomycete bacterium typed as a Nonomuraea species, via a screen for inhibition of growth of the bacterial pathogen Staphylococcus aureus. Thiopeptides are a class of macrocyclic, highly modified peptides that are decorated by thiazoles and defined by a central six-membered heterocyclic ring system. Mining the genomes of thiopeptide-producing strains revealed the elusive biosynthetic route for this class of antibiotics. The thiopeptides are chromosomally encoded, ribosomally synthesized proteins, and isolation of gene clusters for production of thiomuracin and the related thiopeptide GE2270A revealed the post-translational machinery required for maturation. The target of the thiomuracins was identified as bacterial Elongation Factor Tu (EF-Tu). In addition to potently inhibiting a target that is unexploited by marketed human therapeutics, the thiomuracins have a low propensity for selecting for antibiotic resistance and confer no measurable cross-resistance to antibiotics in clinical use.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Staphylococcus aureus
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Tiazoles
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Factor Tu de Elongación Peptídica
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Antibacterianos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Am Chem Soc
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suiza