Spore-derived mycobionts of the lichen Graphis proserpens were cultivated on a malt-yeast extract medium supplemented with 10% sucrose and their metabolites were investigated. Isocoumarin derivatives 1–3 and 7-oxo-5,7-dihydrooxepino[4,3,2-de]isochromene derivatives, proserins A–C (4–6), were isolated along with three known isocoumarin derivatives and three benzoic acid derivatives. Their structures were determined by spectroscopic methods.Graphical abstractSpore-derived mycobionts of the lichen Graphis proserpens were cultivated on a malt-yeast extract medium supplemented with 10% sucrose. From the cultures isocoumarin derivatives 1–3 and 7-oxo-5,7-dihydrooxepino[4,3,2-de]isochromene derivatives, proserins A–C (4–6), were isolated along with six known compounds. Their structures were determined by spectroscopic methods.Highlights► Spore-derived mycobionts of the lichen Graphis proserpens were cultivated. ► Six compounds were isolated from the cultures and their structures were determined. ► Three isocoumarins were closely related to fungal metabolites. ► Proserins possessed a unique 7-oxo-5,7-dihydrooxepino[4,3,2-de]isochromene skeleton.