FAD-binding monooxygenase; part of the gene cluster that mediates the biosynthesis of hypothemycin, a resorcylic acid lactone (RAL) that irreversibly inhibits a subset of protein kinases with a conserved cysteine in the ATP binding site such as human ERK2 (PubMed:18567690). The first step is performed by both PKSs hmp3 and hmp8 and leads to the production of 7',8'-dehydrozearalenol (DHZ) (PubMed:18567690, PubMed:20222707). The highly reducing PKS hpm8 synthesizes the reduced hexaketide (7S,11S,2E,8E)-7,11-dihydroxy-dodeca-2,8-dienoate, which is transferred downstream to the non-reducing PKS hpm3 (PubMed:20222707). Hpm3 then extends the reduced hexaketide to a nonaketide, after which regioselective cyclization and macrolactonization affords DHZ (PubMed:20222707). The next step is the conversion of DHZ into aigialomycin C and is performed by the O-methyltransferase hmp5, the FAD-binding monooxygenase hmp7, and the cytochrome P450 monooxygenase hmp1 (PubMed:18567690). The wide substrate tolerance of the hmp5 and hmp7 implies that the reactions from DHZ to aigialomycin C can occur in any order (PubMed:18567690). The steps from aigialomycin C to hypothemycin are less well established (PubMed:18567690). The FAD-linked oxidoreductase hmp9 presumably catalyzes oxidation of the C-6' hydroxyl to a ketone (PubMed:18567690). The timing of this oxidation is important, since the resulting enone functional group is a Michael acceptor that can react spontaneously with glutathione, an abundant metabolite in fungal cells (PubMed:18567690). The glutathione S-transferase hmp2 catalyzes cis-trans isomerization of the 7',8' double bond with equilibrium favoring the trans isomer (PubMed:18567690). The hpm6-encoded transporter might preferentially pump hypothemycin out of the cell relative to the trans isomer aigialomycin A. The cis-to-trans isomerization may be coupled with C-4' hydroxylation, since all known hypothemycin analogs containing the enone functional group also have hydroxyl groups at both C-4' and C-5' (PubMed:18567690). Binds 1 FAD per subunit. Secondary metabolite biosynthesis. Hypothemycin is an antifungal agent that exhibits excellent activity against Peronophythora litchii, which could be helpful for the storage of harvest litchi fruit (PubMed:24106914). Hypothemycin is a strong inhibitor of a subset of MAP kinases such as human ERK2 (PubMed:18571434, PubMed:20118535, PubMed:26371861). It can therefore be used as an anti-cancer drug thanks to its inhibitory activity of Ras-mediated cellular signals (PubMed:10595743, PubMed:10421424). It can also inhibit Trypanosoma brucei kinase TbCLK1 which is a good candidate as a therapeutic target for African trypanosomiasis (PubMed:23853713). Finally, hypothemycin has also inhibitor activity of T cell activation (PubMed:10598882). Belongs to the FAD-binding monooxygenase family.