Gliotoxin acetate

Gliotoxin (308) is a fungal metabolite, isolated from Aspergillus terreus and found to have antibacterial, antitumor and antifungal effects [18]. Gliotoxin acetate inhibited the CPE of poliovirus in monkey kidney cell cultures due to the early stage inhibition of RNA viral replication [18]. Gliotoxin also inhibits influenza virus-induced RNA polymerase. 

Further proof that all nine carbon atoms of phenylalanine, and not merely the aliphatic side chain, were incorporated into gliotoxin was provided by the isolation of gliotoxin- H after phenylalanine-U- H was added to growing cultures of r. viride. Seventeen percent of the administered tritium-labeled phenylalanine was incorporated into gliotoxin (Winstead and Suhadolnik, I960). These results therefore establish the aromatic amino acid pathway and not the acetate pathway as operative in gliotoxin biosynthesis by T. viride. 

The same group (Kirby et ai, 1978) tested the status of 12 as a free intermediate in T. viride by an intermediate-trapping experiment. Non-radioactive 12 was incubated with the organism and, 2 hr later, L-[t/- C]-phenylalanine was added to the medium. The culture filtrate was extracted with chloroform to remove gliotoxin and then with ethyl acetate to remove the cyclodipeptide (12). This was diluted with pure, inactive 12, and the mixture crystallized to constant " C activity. The residual activity corresponded to 1.3% of that administered as L-[f/- C]phenylalanine. Thus, 12 had been formed from phenylalanine and is presumably present in the organism under normal conditions of growth. It remains to be seen whether... 

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