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

Mass spectrometry-based dereplication and prioritization led to the discovery of four multi--methylated cyclodecapeptides, auyuittuqamides E-H (-), from a soil-derived 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 -based configuration analysis, revealing that - contain both d- and l-isomers of -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 . Bioinformatic analysis identified a putative biosynthetic gene cluster () for auyuittuqamides E-H, and a plausible biosynthetic pathway was proposed. These newly identified fungal cyclodecapeptides (-) displayed growth inhibitory activity against vancomycin-resistant with MIC values of 8 μg/mL.