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

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 H-2 and C-13 isotopically labeled precursors to B. cinerea Delta stc2 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.