The role of nutrition in the synthesis of actinomycin.

Actinomycin, an antibiotic first isolated from a cullture of Streptomyces antibioticus by Waksinan and Woodruff (1940), has since been obtained from fermentations with a number of Streptomyces species. Because of certain differences in the properties of some of the actinomycin products, a series of designations, A, B, C, D, I, J, and X, have been employed to classify them. Each of these substances actually consists of a mixture of closely related biologically active coinponents, (Brockmann and Grone, 1954; Roussos and Vining, 1956; I'ugh et at., 1956). Moreover, the actiniomycin A, B, D, and X complexes may be composed of identical components differing solely in the relative amount of each component present (Roussos and Vining, 1956). Structural studies have revealed that the actinomyciii molecule consists of two polypeptides linked to a chromophoric moiety, 2-aminophenoxaziine-3-onie, which is probably the same for all components (BioCkinan1n et al., 1956; Brockmanin and Vohwinkel, 1956; Bullock and Johnison, 1957). It has been suggeste(l that actinomycin is produced through an oxidative condensation of tw*-o mnolecules of the 3-hydroxy-4methyl anthranilic peptide (Johnson, 1956). The peptides of a given actinomycin may or may not be identical. Further, differences in the comnponents of an actinomycin mixture or of different mixtures are probably due to variations in the number, arrangement, and kinds of amino acids present in the peptides. For example, actinomycin DlV contains D-valine, whereas D-alloisoleucine replaces this amino acid in actinomycin C3 (Brockmann et al., 1956; Bullock and Johnson, 1957). While the chemical nature of certain members of this family of antibiotics has been revealed, almost nothing is known of the mechanism of their biosynthesis. The need for a chemically defined medium to facilitate such studies has led to an investigation of the nutrition of an actinomycin-producing organism, S. antibioticus 3720. The data obtained in such a study are presented in this paper.