Molecular Networking-Based Screening Led to the Discovery of a Cyclic Heptadepsipeptide from an Endolichenic Xylaria sp.

Abstract

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic Xylaria sp. The main component, xylaroamide A (1), was obtained by LC-MS-guided isolation. The planar structure of compound 1 was elucidated via 1D and 2D NMR, as well as MS/MS data. The configurations were fully determined by the combination of advanced Marfey's analysis, partial hydrolysis, Mosher's reaction, and GIAO NMR calculation based on a restricted conformational search. A plausible biosynthetic pathway for xylaroamide A (1) involving a rare trans-acting N-methyltransferase is proposed based on bioinformatics analysis. Xylaroamide A (1) exhibited inhibitory activity against cancer cell lines BT-549 and RKO with IC 50 values of 2.5 and 9.5 μM, respectively.

Japonamides A and B, Two New Cyclohexadepsipeptides from the Marine-Sponge-Derived Fungus Aspergillus japonicus and Their Synergistic Antifungal Activities

“…The absolute configurations of the amino acid moieties in compound 1 were deciphered using the advanced Marfey’s analysis, following HPLC comparison against available l and d commercial standards [ 17 ]. Acid hydrolysis (HCl) of 1 and chemical derivatization with FDAA yielded a mixture of FDAA derivative of Thr (derived from N -Ac- l -Thr), Ile, Pro, N -Me- O -Me-Tyr, and Tyr.…”

“…The minimum pairs’ cosine, matched fragment ions, network topk, maximum connected component size, and cluster size were set to 0.7, 6, 10, 100, and 2, respectively. The results were downloaded and visualized with Cytoscape 3.9.1 [ 17 , 21 ].…”

“…Traditional strategies for mining novel cyclic peptides were not attractive for the repetitive and redundancy discovery of known compounds. Cyclic peptides and depsipeptides often produce characteristic mass fragments for the amide and/or ester bonds in the structure that are susceptible to cleavage during collisions in mass spectrometers [ 17 ]. Molecular networking can automatically group compounds with similar fragmentation patterns according to the tandem mass data and make them visualizable [ 18 ].…”

Chemodiversity and Anti-Leukemia Effect of Metabolites from Penicillium setosum CMLD 18

“…Although recently [ 8 , 21 ], integrated approaches to molecular dereplication have become powerful and efficient strategies for discovering bioactive metabolites [ 22 , 23 , 24 , 25 , 26 , 27 ]. In addition, such tools promote the expansion of fungal and plant chemodiversity.…”

Halogenase-Targeted Genome Mining Leads to the Discovery of (±) Pestalachlorides A1a, A2a, and Their Atropisomers

“…As a part of our efforts to investigate new natural products [ 21 , 22 , 23 , 24 , 25 ], we used the fungal FDH GedL [ 26 ] as a probe to explore the halogenase-containing BGCs from our in-house fungal genome database. A putative halogenase gene, ptlK , was mined from an endolichenic fungus, Pestalotiopsis rhododendri LF-19-12, and further bioinformatics analysis disclosed that ptlK was located in a cryptic BGC ptl .…”