Title:
Inhibition of bacterial undecaprenyl pyrophosphate synthase by small fungal molecules. | Journal:
The Journal of antibiotics. 2016 Nov;69(11):798-805 | Authors:
Inokoshi J, Nakamura Y, Komada S, Komatsu K, Umeyama H, Tomoda H. | 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 IC 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. | | See full PubMed entry: http://www.ncbi.nlm.nih.gov/pubmed/27049441 |
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BRAID