Hassallidin A, a Glycosylated Lipopeptide with Antifungal Activity from the Cyanobacterium Hassallia sp.

Abstract

Hassallidin A (1), a new antifungal glycosylated lipopeptide, was isolated from an epilithic cyanobacterium collected in Bellano, Italy, identified as Tolypothrix (basionym Hassallia) species. Chemical, mass spectrometric, and spectroscopic analyses, including one- and two-dimensional NMR, were performed to determine an esterified eight-residue cyclic peptide linked with a carbohydrate and a fatty acid residue. Chiral GC-MS analysis revealed the occurrence of the nonproteinogenic amino acids d-allo-Thr, d-Thr, d-Tyr, d-Gln, and dehydroaminobutyric acid (Dhb) within the peptide moiety. The additional components of hassallidin A could be identified as α,β-dihydroxytetradecanoic acid (Dht) and mannose. This is the first report on a cyclic peptide of cyanobacterial origin that contains both a fatty acid and a carbohydrate moiety. Compound 1 exhibits antifungal activity against Aspergillus fumigatus and Candida albicans with MIC values of 4.8 μg/mL for both test organisms.