Flavonolignans from Aspergillus iizukae, a Fungal Endophyte of Milk Thistle (Silybum marianum)

Silybin A (1), silybin B (2), and isosilybin A (3), three of the seven flavonolignans that constitute silymarin, an extract of the fruits of milk thistle (Silybum marianum), were detected for the first time from a fungal endophytc, Aspergillus iizukae, isolated from the surface-sterilized leaves of S. marianum. The flavonolignans were identified using a UPLC-PDA-HRMS-MS/MS method by Matching retention times, HRMS, and MS/MS data with authentic reference compounds. Attenuation of flavonolignan production was observed following successive subculturing of the original flavonolignan-producing culture, as is often the case with endophytes that produce plant-based secondary metabolites. However, production of 1 and 2 resumed when attenuated spores were harvested from cultures grown on a medium to which autoclaved leaves of S. marianum were added. The cycle of attenuation followed by resumed biosynthesis of these flavonolignans was replicated in triplicate.