Production, isolation, and properties of azetomycins.

Streptomyces antibioticus synthesizes five actinomycins that differ in the "proline site" of the molecule. When cultured in the presence of azetidine-2-carboxylic acid (AzC), antibiotic synthesis was stimulated 40 to 50%, synthesis of actinomycin IV was inhibited, and one or both prolines were replaced by AzC. AzC incorporation could not be reversed by concomitant supplementation with proline or sarcosine, and only pipecolic acid affected a minor reversal of AzC incorporation. AzC-containing actinomycins were isolated and designated azet-I and azet-II; a third unresolved component or mixture was called azet-III. The molar ratio of AzC to proline was: azet-I, 1:1; azet-II, 2:0. Azet-III was equivocal. These azetidine actinomycins (azetomycins) were found to be potently inhibitory to the growth of selected gram-positive but not as potent to the growth of gram-negative organisms. The relative inhibitory affect against growth and ribonucleic acid synthesis in Bacillus subtilis was: actinomycin IV =/> azet-I > azet-II >>> azet-III. Protein synthesis was affected similarly; however, kinetic studies with B. subtilis revealed that ribonucleic acid synthesis was inhibited rapidly followed by an inhibition of protein synthesis. At concentrations less than 1 mug/ml, deoxyribonucleic acid synthesis was stimulated by these actinomycins.