Sphaerostilbellins, New Antimicrobial Aminolipopeptide Peptaibiotics from Sphaerostilbella toxica

Abstract

Sphaerostilbella toxica is a mycoparasitic fungus that can be found parasitizing wood-decay basidiomycetes in the southern USA. Organic solvent extracts of fermented strains of S. toxica exhibited potent antimicrobial activity, including potent growth inhibition of human pathogenic yeasts Candida albicans and Cryptococcus neoformans, the respiratory pathogenic fungus Aspergillus fumigatus, and the Gram-positive bacterium Staphylococcus aureus. 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’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 μM each for C. neoformans, 1 μM each for A. fumigatus, and 4 and 2 μM, respectively, for C. albicans. Murine macrophage cells were unaffected at these concentrations.

Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum

“…The cytotoxicity of compounds against the macrophage-like murine cell line J774A.1 was evaluated as described previously ( Perlatti, Nichols, Alspaugh, et al, 2020 ). Macrophage J774.1 cells were grown in Dulbecco’s Modified Eagle’s Medium (DMEM) to 70% confluency, harvested, transferred to 96-well tissue culture plates at 10 5 cells well −1 , and incubated overnight at 37°C and 5% CO 2 .…”

Characterization of Microbial Diversity in Decayed Wood from a Spanish Forest: An Environmental Source of Industrially Relevant Microorganisms

“…Previous works indicated the putative antimicrobial activity of microorganisms isolated from decayed wood [11][12][13][14], which fuelled the present analyses of the microbial inhabitants from this non-traditional resource. This study is focused on the detection of genes encoding PKSs and NRPSs, which are involved in the production of different secondary metabolites, such as antibiotics, and the subsequent validation by means of competitive bioassays.…”

“…These complex biological interactions create a highly interesting environmental niche in which to look for microorganism with potential industrial applications in red (e.g., antibiotics, drugs) and white (e.g., enzymes) biotechnologies. Although this niche has not been deeply investigated as a source of antimicrobial compounds, some wood-decaying fungi, or fungi associated with them, present antimicrobial activities [11][12][13]. Besides, different bioactive potential has been described in microorganisms isolated from decaying wood, such as the antimicrobial biosynthetic capacity in Paraburkholderia sp., or anti-insect activity from alkaloids isolated from Penicillium species [14,15].…”

Exploring Peptaibol’s Profile, Antifungal, and Antitumor Activity of Emericellipsin A of Emericellopsis Species from Soda and Saline Soils

“…Peptaibols, the largest group of peptaibiotics, are a class of linear peptides that have an acylated N terminus group, a C-terminal amino acid, and a high content of α-aminoisobutyric acid (Aib)—approximately 40% of Aib in long peptaibols and from 14 to 56% in short peptaibols [ 7 , 11 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Peptaibols are dominant secondary metabolites of filamentous fungi including the ones exhibiting a mycoparasitic lifestyle [ 22 , 24 , 25 , 29 , 30 ].…”