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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, PubMed:28240554). 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 (PubMed:26978228, PubMed:28240554). Subsequent intramolecular deprotonation of C3 phenolic oxygen accelerates phenalenone ring closure to yield the tricyclic phenalenone core with a C2 hydroxylation (PubMed:26978228, PubMed:28240554). The prenyltransferase phnF further catalyzes reverse C-prenylation of phenalenone by direct electrophilic substitution at C6, or possibly via first a forward O-prenylation of a neighboring phenol in phenalenone, followed by a Claisen rearrangement (PubMed:28240554). The hydroalkoxylation enzyme phnH catalyzes the 5-exo-trig cyclization via acid catalysis after the spontaneous deprotonation of 7-OH, which leads to the formation of the dihydrobenzofuran atrovenetin (PubMed:28240554). Atrovenetin is further converted to deoxyherqueinone by the O-methyltransferase phnC which can methylate C2-OH to stabilize the northern portion of the phenalenone core (PubMed:28240554). Finally, the oxidoreductase phnG converts deoxyherqueinone to herqueinone via C6 hydroxylation (PubMed:28240554)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"2,4,7,9-tetrahydroxy-6-methyl-8-(2-methylbut-3-en-2-yl)-1-oxo-1H-phenalen-3-ol = (2'R)-atrovenetin","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:62660"},{"database":"ChEBI","id":"CHEBI:145870"},{"database":"ChEBI","id":"CHEBI:145872"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28240554"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:62661"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28240554"}]}]},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":216.0,"unit":"uM","substrate":"the atrovenetin 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