Fungal Coculture\nof <i>Herpotrichia</i> sp.\nand <i>Trametes versicolor</i> Induces Production of Diverse\nMetabolites with Anti-Parkinson’s Neuroprotective Activity

Co-cultivation of isopod-associated fungi <i>Herpotrichia</i> sp. SF09 and <i>Trametes versicolor</i> SF09A led to the\nreciprocal induction of thirteen new compounds (<b>1</b>–<b>7</b> and <b>9</b>–<b>13</b>) with diverse\narchitectures. Importantly, compounds <b>1</b> and <b>2</b> are rare fungal sesquiterpene-saccharide hybrids incorporating a\nxylopyranose moiety, compound (±)-<b>3</b> represents the\nfirst example of a natural linear sesquiterpene racemate, and compound <b>7</b> is a rare α-pyrone derivative with a xylopyranose\nmotif. Their structures were elucidated by analysis of NMR and mass\nspectrometry data, and their absolute configurations were determined\nby Mosher’s method, microscale derivatization, and single-crystal\nX-ray diffraction, as well as ECD calculations. All the isolated compounds\nameliorated MPP<sup>+</sup>-induced oxidative damage in PC12 cells\nin a dose-dependent fashion. Among them, compounds <b>5</b> and <b>15</b> showed significant protective action against neuronal injury\nby MPP<sup>+</sup> at 5 μM. Meanwhile, transcriptome sequencing\nwas performed to evaluate the molecular mechanism of the neuroprotective\nactivity for compound <b>5</b>. Results indicated that compound <b>5</b> might mitigate MPP<sup>+</sup>-induced neuronal injury through\nthe regulation of multiple signaling pathways, including the PI3K-Akt\nand MAPK pathways. Our findings suggested that compound <b>5</b> could be a promising neuroprotective agent for the treatment of\nParkinson’s disease.