Quinoisobutyride A, an acyclic antibacterial tetrapeptide incorporating an unprecedented heterocyclic amino acid residue from the hypersaline lake-derived fungus Penicillium simplicissimum strain WSH17

Abstract

Chromatographic refining of the EtOAc extract of a solid rice culture of the hypersaline lake-derived fungus Penicillium simplicissimum strain WSH17 afforded a new linear antibacterial peptide quinoisobutyride A (1) along with three known metabolites (2-4). The chemical structure of 1 was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses together with HRESIMS. In addition, Marfey's derivatization method along with biogenetic considerations were used to determine the absolute configuration of its amino acids’ entities. Interestingly, in this study we distinguished a new unusual heterocyclic amino acid which is comprised as a unit of compound 1. Among the isolated compounds, only 1 revealed a promising antibacterial activity against Staphylococcus aureus (ATCC700699) with a MIC value of 2.72 μM (2.0 μg/mL). Moreover, citrinamide A (3) was the only isolated compound that showed a cytotoxic activity against human epithelial colorectal adenocarcinoma (Caco-2) cell line with an IC50 value of 12.76 μM (5.5 μg/mL).