Sphaerostilbellins, New Antimicrobial Aminolipopeptide Peptaibiotics from Sphaerostilbella toxica

Abstract

<i>Sphaerostilbella toxica</i> is a mycoparasitic fungus that can be found parasitizing wood-decay basidiomycetes in the southern USA. Organic solvent extracts of fermented strains of <i>S. toxica</i> exhibited potent antimicrobial activity, including potent growth inhibition of human pathogenic yeasts <i>Candida albicans</i> and <i>Cryptococcus neoformans,</i> the respiratory pathogenic fungus <i>Aspergillus fumigatus</i>, and the Gram-positive bacterium <i>Staphylococcus aureus</i>. Bioassay-guided separations led to the purification and structure elucidation of new peptaibiotics designated as sphaerostilbellins A and B. Their structures were established mainly by analysis of NMR and HRMS data, verification of amino acid composition by Marfey&rsquo;s method, and by comparison with published data of known compounds. They incorporate intriguing structural features, including an N-terminal 2-methyl-3-oxo-tetradecanoyl (MOTDA) residue and a C-terminal putrescine residue. The minimal inhibitory concentrations for sphaerostilbellins A and B were measured as 2 &mu;M each for <i>C. neoformans</i>, 1 &mu;M each for <i>A. fumigatus</i>, and 4 and 2 &mu;M, respectively, for <i>C. albicans</i>. Murine macrophage cells were unaffected at these concentrations.