Branched-Chain Amino Acid Substitutions in the Biosynthesis of the Antibiotic Actinomycin

Actinomycins normally contain N-methyl-l-valine and either d-valine, d-alloisoleucine or both amino acids in the molecule. During antibiotic formation in a medium supplemented with one of the four isoleucine stereoisomers, Streptomyces parvulus and S. chrysomallus form complex actinomycin mixtures (C(1), C(2), C(3), E(1), and E(2)-like compounds). Although chromatographic techniques suggested that single homogeneous components had been isolated, subsequent studies indicated that such chromatographic fractions probably consisted of multiple isomers of actinomycin. Amino acid analyses revealed the presence of N-methylvaline and/or N-methylalloisoleucine and, in addition, d-isoleucine, d-valine, and d-alloisoleucine were frequently found in a given fraction.