Cyclopeptide\nAvellanins D–O with Antimalarial\nActivity from the Mariana Trench Anemone-Derived <i>Hamigera\ningelheimensis</i> MSC5

Marine\nmicroorganisms are a treasure trove of natural products,\nespecially those in extreme marine environments, which may produce\nnovel natural products. Herein, biosynthetic gene cluster analysis\ncombined with an integrated metabolomic strategy incorporating matrix-assisted\nlaser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF\nMS), nuclear magnetic resonance (NMR), and liquid chromatography–mass\nspectrometry/mass spectrometry (LC-MS/MS) based Global Natural Products\nSocial Molecular Networking (GNPS) was used to discover new compounds\nfrom the Mariana trench anemone-derived fungus <i>Hamigera ingelheimensis</i> MSC5. As a result, 12 new cyclic pentapeptides, avellanins D–O\n(<b>1</b>–<b>12</b>), were isolated, together with\na known cyclic pentapeptide avellanin C (<b>13</b>). All the\nstructures and absolute configurations were elucidated using NMR,\nmass spectrometry, X-ray diffraction analysis, and Marfey’s\nmethod. A plausible biosynthetic pathway for the avellanins was proposed\nbased on the gene cluster analysis of <i>H. ingelheimensis</i> MSC5. Bioassay revealed that compound <b>6</b> exhibited potent\nantimalarial activity with an IC<sub>50</sub> value of 0.19 ±\n0.09 μM.