The biosynthetic incorporation of [phenyl-3H]phenylalanine into gliotoxin

Abstract

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.