Studies on the biosynthesis of phenols in fungi. Biosynthesis of 3,4-dimethoxy-6-methyltoluquinol and gliorosein in Gliocladium roseum I.M.I. 93 065.

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1. Gliorosein was obtained in excellent yield (150mg./200ml. of Raulin-Thom medium) from surface cultures of Gliocladium roseum. Its nuclear-magnetic-resonance spectrum showed conclusively that it is 1,6-dihydro-3,4-dimethoxy-6-methyltoluquinone. 2. Sodium [2-(14)C]acetate was incorporated into gliorosein and the related products (3.3% conversion). The specific activities of these substances increased in the order gliorosein, 3,4-dimethoxy-6-methyltoluquinol, the related quinhydrone and quinone, indicating that gliorosein was the actual metabolite that was secreted and that the other compounds were derived from it in the medium. 3. 6-Methylsalicylic acid was not taken up by the mycelium and could be recovered unchanged. Orsellinic acid was decarboxylated by G. roseum and an equivalent amount of orcinol was secreted into the medium. The methyl esters of 6-methylsalicylic acid and orsellinic acid were both hydrolysed by an esterase present in the mycelium. Some of the 6-methylsalicylic acid thus produced was secreted into the medium and the orsellinic acid was decarboxylated. 4. Washed mycelium of G. roseum converted aurantiogliocladin and 3,4-dimethoxy-6-methyltoluquinol quantitatively into gliorosein within 18hr. More critical experiments with (14)C-labelled substrates demonstrated that 3-hydroxy-4-methoxy-6-methyltoluquinol and 3,4-dimethoxy-6-methyltoluquinol, and their respective quinones, were effectively incorporated into gliorosein and related products (49, 68, 30 and 57% respectively). 5. The following sequence of reactions is proposed for the biosynthesis of gliorosein: acetyl-CoA+3 malonyl-CoA+S-adenosyl-methionine --> 5-methylorsellinic acid --> 3-hydroxy-4-methoxy-6-methyltoluquinol --> 3,4-dimethoxy-6-methyltoluquinol --> gliorosein. 6. Since gliorosein is optically active (dextrorotatory), the final tautomerization reaction leading to its formation must be enzyme-catalysed.