Cyclopeptide Avellanins D-O with Antimalarial Activity from the Mariana Trench Anemone-Derived MSC5.

Marine microorganisms are a treasure trove of natural products, especially those in extreme marine environments, which may produce novel natural products. Herein, biosynthetic gene cluster analysis combined with an integrated metabolomic strategy incorporating matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) based Global Natural Products Social Molecular Networking (GNPS) was used to discover new compounds from the Mariana trench anemone-derived fungus MSC5. As a result, 12 new cyclic pentapeptides, avellanins D-O (-), were isolated, together with a known cyclic pentapeptide avellanin C (). All the structures and absolute configurations were elucidated using NMR, mass spectrometry, X-ray diffraction analysis, and Marfey's method. A plausible biosynthetic pathway for the avellanins was proposed based on the gene cluster analysis of MSC5. Bioassay revealed that compound exhibited potent antimalarial activity with an IC value of 0.19 ± 0.09 μM.