Inhibition of bacterial undecaprenyl pyrophosphate synthase by small fungal molecules.
J Antibiot (Tokyo)
; 69(11): 798-805, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27049441
ABSTRACT
Viridicatumtoxin and spirohexaline, small fungal molecules with a tetracyclic scaffold and an additional spirobicyclic ring in common, were found to inhibit bacterial undecaprenyl pyrophosphate (UPP) synthase with IC50 values of 4 and 9 µm, respectively. These molecules showed weak inhibitory activity against catalytically related enzymes such as bacterial octaprenyl pyrophosphate synthase and yeast dehydrodolichyl pyrophosphate synthase, indicating that the compounds preferentially inhibit UPP synthase. They showed antimicrobial activity, particularly against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, molecular modeling strongly suggested that the hydrophobic spirobicyclic ring of viridicatumtoxin interacts with three hydrophobic clefts of the active site in MRSA UPP synthase.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Espiro
/
Alquil e Aril Transferases
/
Fungos
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Antibacterianos
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Micotoxinas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article