APPLICATION OF STABLE ISOTOPE LABELLING METHODOLOGY TO THE BIOSYNTHESIS OF THE MYCOTOXIN, TERRETONIN, BY ASPERGILLUS TERREUS: INCORPORATION OF (13)C-LABELLED ACETATES AND METHIONINE, (2)H- AND (13)C, (18)O-LABELLED ETHYL 3,5-DIMETHYLORSELLINATE AND OXYGEN-18 GAS

Article abstract of DOI:10.1016/S0040-4020(01)83433-5

Incorporation of (13)C-labelled acetates and methionine, (14)C and (2)H-labelled ethyl 3,5-dimethylorsellinate into terretonin (5) by cultures of Aspergillus terreus indicated that its biosynthesis proceeds via a mixed polyketide-terpenoid (meroterpenoid) pathway.Incorporation of (18)O2 gas and ethyl 3,5-dimethylorsellinate (7) doubly labelled with (13)C and (18)O in the carbonyl of the carboxyl group and at the C-6 position into terretonin (5) and observation of (18)O isotope-induced shifts in the (13)C n.m.r. spectra and GC/MS studies of the enriched metabolites determined the origin of all of the oxygen atoms in (5) and provided mechanistic insight into the biosynthetic pathway.