Structural and biosynthetic studies of botrycinereic acid, a new cryptic metabolite from the fungus Botrytis cinerea

• Botrycinereic acid is a new cryptic metabolite from Botrytis cinerea. • Botrycinereic acid was obtained by chemical epigenetic manipulation of B. cinerea with SAHA. • Botrycinereic acid was overproduced by inactivating the stc2 gene of B. cinerea B05.10. • Botrycinereic acid is biosynthesized from l -phenylalanine and l -leucine. Chemical epigenetic manipulation of Botrytis cinerea strain B05.10 with the histone deacetylase inhibitor SAHA led to the isolation of a new cryptic metabolite, botrycinereic acid ( 22a ). This compound was also overproduced by inactivating the stc2 gene, which encodes an unknown sesquiterpene cyclase. Its structure and absolute configuration were determined by extensive spectroscopic NMR and HRESIMS studies, and electronic circular dichroism calculations. Its biosynthesis was studied by feeding 2 H and 13 C isotopically labeled precursors to B. cinerea Δstc2 mutant. A detailed analysis of the labeling and coupling patterns into botrycinereic acid ( 22a ) revealed that this compound derives from l -phenylalanine and l -leucine.