Mass Spectrometry-Guided Discovery of Multi-N-Methylated Cyclodecapeptides Auyuittuqamides E-H from Sesquicillium sp. QL0466

Mass spectrometry-based dereplication and priori-tization led to the discovery of four multi-N-methylated cyclo-decapeptides, auyuittuqamides E-H (1-4), from a soil-derived Sesquicillium sp. The planar structures of these compounds were elucidated based on analysis of HRESIMS and NMR data. Absolute configurations of the chiral amino acid residues were assigned by a combination of the advanced Marfey's method, chiral-phase LC-MS analysis, and J-based configuration analysis, revealing that 1-4 contain both D- and L-isomers of N- methylleucine (MeLeu). Differentiation of D- and L-MeLeu in the sequence was achieved by advanced Marfey's analysis of the diagnostic peptide fragments generated from partial hydrolysis of 1. Bioinformatic analysis identified a putative biosynthetic gene cluster (auy) for auyuittuqamides E-H, and a plausible biosynthetic pathway was proposed. These newly identified fungal cyclodecapeptides (1-4) displayed in vitro growth inhibitory activity against vancomycin-resistant Enterococcus faecium with MIC values of 8 mu g/mL.