Fig. 6: Proposed biosynthetic pathway for oxpinamide F in Aspergillus ustus.

Ant, l-Phe and l-Ile are assembled to protuboxepin K (3) by the NRPS OpaA with epimerization at the phenylalanyl residue. The oxepinase OpaB catalyzes the oxepin ring formation in protuboxepin A (4). The regio- and stereospecific hydroxylation of 4 by OpaC is accompanied by a double bond migration, leading to the conversion of a 1H-oxepin to a 3H-oxepin system in 5. The d-Phe configuration in 5 is changed to l-Phe in 2 by the single epimerase OpaE. The O-methyltransferase OpaF catalyzes the conversion of 2 to the end product 1 by methylation of the hydroxyl group at C-12.