Fruiting Liquid of Mushroom-Forming Fungi, A Novel Source of Bioactive Compounds - Fruiting-Body Inducer and HIF and Axl Inhibitors

In general, mushroom-forming fungi secrete liquid on the surface of mycelia just before fruiting-body formation. However, no researchers in mushroom science have paid attention to the liquid until now. We formulated a hypothesis that the liquid plays an important role(s) in the formation of the fruiting body and produces various bioactive compounds and named it the fruiting liquid (FL). Four novel compounds (1-4) were isolated from FL of Hypholoma lateritium and Hericium erinaceus . The structures of 1-4 except for their stereochemistry were determined by interpretation of MS and NMR data. The absolute configurations of compounds 1-4 were determined by quantum chemical calculation of the ECD spectrum, by single-crystal X-ray diffraction analyses, or by chemical syntheses. Compounds 1, 3, and 4 induced fruiting body formation of Flammulina velutipes . Compound 4 inhibited the activity of hypoxia-inducible factor, and compounds 2-4 suppressed receptor tyrosine kinase (Axl) expression.

Automated summary

Mushroom-forming fungi secrete liquid on mycelia surface before fruiting-body formation, which has been overlooked by mushroom researchers. We hypothesize that this liquid, called the fruiting liquid (FL), plays a crucial role in fruiting body formation and produces bioactive compounds. Four novel compounds (1-4) were isolated from FL of two mushroom species, with their structures determined through various methods. Compounds 1, 3, and 4 induced fruiting body formation in a different mushroom species, while compound 4 showed inhibitory effects on hypoxia-inducible factor and compounds 2-4 suppressed the expression of receptor tyrosine kinase (Axl).