FACTORS AFFECTING STREPTOMYCIN YIELDS

Abstract

ALTHOUGH HIGH YIELDS of a desired fermentation product can often be obtained by empirical manipulations of the environment in which a given organism is expected to be productive, it is more satisfying scientifically to base such control, if possible, on a closer acquaintance with the nature of the fermentation. For instance, high yields of penicillin are accompanied by characteristic metabolic changes in the medium; both can be attained by changing the physical or chemical milieu of the organism (cf. Jarvis and Johnson, 1947). Early experiments with Streptomyces griseus seemed to support the hypothesis that streptomycin production would follow a similar pattern (Garner et al., 1950); however, subsequent results showed that the relation between high streptomycin yields and gross metabolism, at least as embraced by our studies, was obscure more often than not. Waksman et al. (1946) first reported some of the changes occurring, during growth of a streptomycinproducing organism. They found a gradual rise in pH of the culture on a glucose, peptone, meat extract medium, and an increase in ammonia and amino nitrogen; accumulation of streptomycin paralleled the growth of the organism. Gottlieb and Anderson (1947) used a vegetative inoculum, which gives more rapid growth, and found that the peak of streptomycin production lagged behind the growth peak. Synthesis of streptomycin proceeded only in the presence of oxygen, and there was no correlation between pH changes and streptomycin production. Dulaney and Perlman (1947) compared the chemical changes that occurred during the submerged growth of organisms in Waksman's medium and media that contained high levels of either phosphate or carbohydrate. The growth phase was accompanied by reduction of soluble medium constituents, a high oxygen demand, and little streptomycin production. This was followed by an autolytic phase in which inorganic phosphorus and soluble nitrogen were released, the oxygen demand dropped, and streptomycin was produced. Added phosphate reduced streptomvcin yields, while high levels of carbohydrate had little effect aside from prolonging the growth phase. We have isolated a culture capable of giving relatively high yields and have attempted to analyze