6-hydroxymellein synthase; part of the gene cluster that mediates the biosynthesis of terrein, a fungal metabolite with ecological, antimicrobial, antiproliferative, and antioxidative activities (PubMed:24816227). The first step in the pathway is performed by the polyketide synthase terA that produces 4-hydroxy-6-methylpyranon (4-HMP), orsellinic acid (OA), and 2,3-dehydro-6-hydroxymellein (2,3-dehydro-6-HM) by condensing acetyl-CoA with two, three, or four malonyl-CoA units, respectively (PubMed:24816227). 4-HMP and OA are not pathway intermediates, but are rather shunt or side products (PubMed:24816227). 2,3-dehydro-6-HM is further converted to 6-hydroxymellein (6-HM) by the 6-hydroxymellein synthase terB (PubMed:24816227). The monooxygenases terC and terD, the multicopper oxidase terE and the Kelch-like protein terF are then involved in the transformation of 6-HM to terrein (PubMed:24816227). Even if they are co-regulated with the other terrein cluster genes, terH and terI seem to be dispensable for terrein production; whereas one or both of the 2 transporters terG and terJ are probably required for efficient secretion of metabolites (PubMed:24816227). Secondary metabolite biosynthesis. Expression is induced by methionine (PubMed:26173180). Nitrogen starvation induces expression of terB and promotes terrein production during fruit infection, via regulation by areA and atfA (PubMed:26173180). Iron limitation acts as a third independent signal for terrein cluster induction via the iron response regulator hapX (PubMed:26173180). Finally, expression is under the control of the terrein cluster-specific transcription factor terR (PubMed:25852654). Impairs the production of terrein (PubMed:24816227). Terrein shows anticancer activity on various tumors including cervical carcinoma, ovarian cancer, and head and neck cancer (PubMed:23417151, PubMed:25318762, PubMed:27127118, PubMed:25592371). The secondary metabolite acts as angiogenesis inhibitors through the inhibition of angiogenin secretion (PubMed:18776656, PubMed:27127118). Terrein has also anti-inflammatory activity (PubMed:18358890). It shows an alleviative function of age-related inflammation characterized as an anti-oxidant and might therefore be a useful nutraceutical compound for anti-aging (PubMed:26416516). Terrein may enhance osseointegration by decreasing the level of ROS and has a potentially synergistic effect on osteoblast differentiation (PubMed:21104936). Terrein has also been shown to act as a melanogenesis inhibitor (PubMed:15558216, PubMed:15603975, PubMed:19493001).