Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules.
J Am Chem Soc
; 136(26): 9244-7, 2014 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-24932672
ABSTRACT
The gene cluster responsible for synthesis of the unknown molecule "colibactin" has been identified in mutualistic and pathogenic Escherichia coli. The pathway endows its producer with a long-term persistence phenotype in the human bowel, a probiotic activity used in the treatment of ulcerative colitis, and a carcinogenic activity under host inflammatory conditions. To date, functional small molecules from this pathway have not been reported. Here we implemented a comparative metabolomics and targeted structural network analyses approach to identify a catalog of small molecules dependent on the colibactin pathway from the meningitis isolate E. coli IHE3034 and the probiotic E. coli Nissle 1917. The structures of 10 pathway-dependent small molecules are proposed based on structural characterizations and network relationships. The network will provide a roadmap for the structural and functional elucidation of a variety of other small molecules encoded by the pathway. From the characterized small molecule set, in vitro bacterial growth inhibitory and mammalian CNS receptor antagonist activities are presented.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Escherichia coli
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Bibliotecas de Moléculas Pequenas
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Metabolômica
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Policetídeos
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos