Studies on the biosynthesis of quinones in fungi. Incorporation of 6-methylsalicylic acid into fumigatin and related compounds in Aspergillus fumigatus I.M.I. 89353

1. Orsellinic acid has been detected as a metabolite of Aspergillus fumigatus. 2. The other principal aromatic components of the medium are fumigatin and the quinol, fumigatol. Fumigatol has been shown to be dihydrofumigatin after oxidation to the quinone followed by acetylation. 3. (14)C-labelled 6-methylsalicylic acid can be hydroxylated in A. fumigatus to form orsellinic acid and decarboxylated to give m-cresol. 4. (14)C-labelled 6-methylsalicylic acid is incorporated into fumigatin and fumigatol (1.0-1.5%), but the conversion does not occur until about 2-3 days after supplementation of the medium. At this stage of growth, the organism has already synthesized approx. 20 times as much fumigatol as fumigatin and this ratio is reflected in the much lower specific activity of the quinol. 5. Supplementation of the medium with either orsellinic acid or orcinol, in addition to (14)C-labelled 6-methylsalicylic acid, greatly decreases the latter's incorporation into fumigatin. At the same time, the cultures containing these substances are stimulated to produce another quinone with relatively high specific activity. 6. 6-Methylsalicylic acid has not been detected in the medium of normal cultures. The results indicate that 6-methylsalicylic acid itself is not a direct precursor of fumigatin and fumigatol but that it is converted into a true intermediate, probably after hydroxylation to orsellinic acid. 7. Supplementation of the medium with 6-methylsalicylic acid (15-25mg./200ml.) greatly affects the metabolism of A. fumigatus. Growth is inhibited and the synthesis of fumigatol is markedly depressed in these cultures. The inhibitory effects may possibly be related in some way to the production of m-cresol.