PRODUCTION OF ANTIBIOTIC SUBSTANCES BY ACTINOMYCETES *†

It has now been definitely established that a considerable proportion of all actinomycetes that can be isolated from soils or other natural substrates have the capacity of inhibiting the growth of, and even of destroying, bacteria and other microorganism.5 This was brought out emphatically in several of the surveys that have been made on the distribution of antagonistic properties among actinomycetes.1, 2, 4, 6, 10 Twenty to 50 per cent of all the cultures tested, whether freshly isolated from natural substrates or taken from culture collections, were found to possess antagonistic properties. The selective antimicrobial activities of actinomycetes differ greatly, both quantitatively and qualitatively, as could easily be demonstrated by their respective antibiotic spectra. The nature of the active agents or the antibiotics produced by these organisms depends upon the species; frequently upon the strain; the composition of the medium in which it is grown, and the conditions of cultivation.7, 8 Several distinct antibiotics have now been isolated from cultures of actinomycetes. Some, namely, actinomycetin, micromonosporin, mycetin, and actinomyces lysozyme, have been only partly purified, whereas others, including actinomycin, proactinomycin, streptothricin, and streptomycin, have been isolated and crystallized. These substances differ greatly in their chemical structure, antimicrobial properties, toxicity to animals, and in vivo activity. Some of the antibiotics are produced in simple synthetic media; others are formed in complex organic substrates; still others, like streptomycin, require the presence in the medium of a specific nutritive substance, an “activity factor,” which is either a precursor or a prosthetic group of an enzyme system essential for the production of the antibiotic agent. Although this “activity factor” can be synthesized by Streptomyces griseus, its addition to the medium favors the rapid production of streptomycin. Streptomyces griseus can, therefore, grow