Structures and Antifungal Activities of New Aureobasidins.

The Journal of Antibiotics
1995.0

Abstract

Aureobasidins (Ab's) are antifungal antibiotics produced by Aureobasidium pullulans R106, with over 20 congeners (e.g., AbA) structured as cyclic depsipeptides containing eight amino acids (three or four N-methylated) and one hydroxy acid. We discovered six new congeners (AbT1-T4, AbU1-U2) and report their isolation, structures, and antifungal activities. The fermentation broth was treated with ethanol, then purified using HP-40 resin, silica-gel column, and ODS-silica HPLC. Structures were determined via amino acid analysis, high-resolution fast atom bombardment mass spectrometry (HRFAB-MS), and stereochemical analysis (chiral columns), revealing specific substitutions relative to AbA: AbT1 contains (2R,3S)-2-hydroxy-3-methylpentanoic acid [(2R,3S)-Hmp] at position 1; AbT2 has N-methylleucine (MeLeu) at position 7; AbT3 has D-2-hydroxyisovaleric acid (D-Hiv) at position 1, β-hydroxy-N-methylphenylalanine (βHOMePhe) at position 4, and N-methylvaline (MeVal) at position 9; AbT4 has N-methylalloisoleucine (Mealle) at position 7; AbU1 has valine (Val) at position 2; AbU2 has D-Hiv at position 1 and Val at position 2. Antifungal activity assays (minimum inhibitory concentration, MIC) showed AbT1 had higher activity against Candida albicans than AbA (MIC 0.0125 vs. 0.05 μg/ml), AbU1 had the lowest activity (MIC 0.78 μg/ml), and AbT3 was the most active among congeners lacking β-hydroxy-N-methylvaline (βHOMeVal) at position 9. N-methyl groups at positions 2 and 7 are critical for the high antifungal activity of Ab's, while the role of βHOMePhe in AbT3 contradicted previous findings with AbR (which showed little activity despite having βHOMePhe and MeVal).

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