Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Both a face-selective and a non-face-selective mode of formation of quaternary centers of isoprene-derived structural moieties of the natural alkaloid paraherquamide A (1) have been discovered by feeding experiments on Penicillium fellutanum with [U-¹³ C₆ ]-glucose and [¹³ C₂ ]-acetate. The labeling patterns suggest that the methyl groups (C22, C23) are introduced in a non-face-selective manner by a reverse prenyl transferase. The C₅ unit comprising the dioxepin moiety retains stereochemical integrity indicative of a single, face-selective addition of the phenolic group to the dimethylallyl group.