Fungal Coculture of Herpotrichia sp. and Trametes versicolor Induces Production of Diverse Metabolites with Anti-Parkinson’s Neuroprotective Activity

作者：Zi-Jue Wang, Yirui Hong, Xinyu Wang, Jingzhe Wang, Yi‐Jie Zhai, Wei Cui, Wenbo Han · 发表于：Journal of Natural Products · 年份：2024 · DOI：10.1021/acs.jnatprod.4c00421 · 被引用次数：6 · 研究领域：Chemical synthesis and alkaloids、Fungal Biology and Applications、Microbial Natural Products and Biosynthesis

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