Function
Dehydratase; part of the gene cluster that mediates the biosynthesis of phenalenones such as herqueinone, compounds that have been reported to treat tumors, bacterial infections and/or mycoses, and rheumatic diseases (PubMed:26978228). The non-reducing polyketide synthase phnA synthesizes the heptaketide backbone and cyclizes it into the angular, hemiketal-containing naphtho-gamma-pyrone prephenalenone. The product template (PT) domain of phnA catalyzes only the C4-C9 aldol condensation, which is unprecedented among known PT domains (PubMed:26978228). The transformation of prephenalenone to phenalenones requires an FAD-dependent monooxygenase phnB, which catalyzes the C2 aromatic hydroxylation of prephenalenone and ring opening of the gamma-pyrone ring simultaneously. Subsequent intramolecular deprotonation of C3 phenolic oxygen accelerates phenalenone ring closure to yield the tricyclic phenalenone core with a C2 hydroxylation (PubMed:26978228). The remaining tailoring enzymes encoded in the gene cluster involved in the biosynthesis of herqueinone include the O-methyltransferase phnC which can methylate C2-OH to stabilize the northern portion of the phenalenone core, the prenyltransferase phnF, which installs the dimethylallyl group at C5, and the oxidoreductase phnG which can further hydroxylate C6. Formation of the fused tetrahydrofuran moiety may require an additional enzyme and may involve those of unassigned function in or immediately adjacent to the gene cluster (Probable).