The biosynthetic incorporation of [phenyl-3H]phenylalanine into gliotoxin
When mixtures of DL-[2′,4′,6′-3H3]-m-tyrosine and DL-[1-14C]phenylalanine were fed to cultures of Gliocladium deliquescens good incorporation (4.9 and 1.6% in separate experiments) of 14C and negligible incorporation (ca. 0.04%) of 3H into the derived gliotoxin (2) was observed. Incorporation of DL-[1-14C, 3′-3H]-, DL-[1-14C, 2′-3H]-, and L-[1-14C, 4′-3H]-phenylalanine into gliotoxin occurred without loss of tritium. Degradation of the [14C, 3H]gliotoxin gave, in each case, bis(anhydro-dethio) gliotoxin (3) and dehydrogliotoxin (4) having a tritium content indicating that the incorporation of phenylalanine had occurred without migration of tritium. These results, taken together, show that neither m-tyrosine (3′-hydroxyphenylalanine) nor any other hydroxybenzene derivative can be an obligatory intermediate on the biosynthetic pathway from phenylalanine to gliotoxin. The possible involvement of arene oxides in gliotoxin biosynthesis is discussed.