Arising from a search for new inhibitors of bacterial fatty
acid biosynthesis, the 2-pyrone-containing natural products
pseudopyronines A (1) and B (2) were recently reported as
mild antibiotics.17,18 The compounds, detected using a lacZ reporter
cell-based assay, were isolated from fermentation of Pseudomonas
sp. F92S91, which was itself isolated from a sponge
collected in Fiji. Pyrone 2 had previously been reported as
Sch 419560, identified from fermentation extracts of Pseudomonas
fluorescens.19 Pseudopyronines A and B inhibited the
growth of Gram-positive bacteria, including Bacillus subtilis,
methicillin-resistant Staphylococcus aureus, Moraxella catarrhalis
and Enterococcus faecium (MIC 1e64 mg/mL) with pseudopyronine
B being the more active of the two compounds.
Pseudopyronine B (2) inhibited the cellular uptake and incorporation
of thymidine, uridine and amino acids suggestive of
a mode of action related to the disruption of membrane function.
17 Notably, pseudopyronine B showed neither a membrane-
damaging effect on human red blood cells nor caused
haemolysis, indicating selectivity for bacterial membranes.