Biosynthesis of the actinomycin chromophore. Influence of α-, 4-, 5-, and 6-methyl- DL-tryptophan on actinomycin synthesis

Abstract

Actinomycin synthesis by growing cells and washed suspensions of Streptomyces antibioticus was inhibited by α-, 4-, 5-, and 6-methyl- DL-tryptophan: the order of their effectiveness was found to be α- > 4- > 5- > 6- methyl- DL-tryptophan . The inhibition of synthesis observed with α-methyl- and 4-methyltryptophan was readily reversed by L-tryptophan and L-kynurenine; 3-hydroxy- DL-kynurenine and 3-hydroxyanthranilic acid were effective also in reversing the α-methyl analog inhibition. It was concluded that the antimetabolites block antibiotic formation by interfering with the synthesis or metabolism of tryptophan, an important precursor in the biosynthesis of the actinomycin chromophore.