STREPTOMYCIN FORMATION BY INTACT MYCELIUM OF STREPTOMYCES GRISEUS

Abstract

NoMI, RYOSAKU (Rutgers, The State University, New Brunswick, N.J.). Streptomycin formation by intact mycelium of Streptomyces griseus. J. Bacteriol. 86:1220-1230. 1963.-A study was made of streptomycin formation by intact mycelium of Streptomyces griseus 107 grown in glucose-yeast extract medium. When mycelium harvested after 24, 48, and 72 hr was compared, the earliest growth showed the highest activity in producing streptomycin from glucose. The concentration of streptomycin in the mycelium was higher in the older growth. Calcium chloride had a remarkable effect in increasing streptomycin production from the precursors in the mycelium, especially when the mycelium was grown for 48 hr or longer. The effect of calcium chloride cannot be attributed to the precipitation of an excess of inorganic phosphate in the medium. Glucose, fructose, glycerol, lactic acid, glucosamine, streptidine, and inositol stimulated streptomycin formation, whereas gluconic acid, glucuronic acid, streptamine, and strepturea did not. When 24-hr-old mycelium was suspended and shaken in 0.5% glucose solution, the antibiotic precursors necessary to produce streptomycin were found mainly in the supernatant of the culture rather than in the mycelium. The supernatant included some substance which had a weak antibiotic activity. This substance was less basic than streptomycin and was transformed to streptomycin with a remarkable increase in antibiotic activity. Numerous investigations have been published dealing with the formation of streptomycin by various strains of Streptomyces griseus in growing culture, the conditions of its formation, and the effect of culture media, organic and inorganic compounds, and special supplements. The my

Biochemistry and regulation of streptomycin and mannosidostreptomycinase (alpha-D-mannosidase) formation.

“…The role of calcium in stimulating streptomycin production could be due to reversal of the effects of high phosphate concentrations introduced in complex additives (45). Calcium has been reported to increase the reproducibility of experiments, presumably by retarding lysis of mycelia (49,85). The need for Mn+ is controversial.…”

“…In addition to complete fermentations, streptomycin can be synthesized by "resting" mycelial suspensions (85,103,105). In such systems, the optimum pH for streptomycin production is 6.5 to 7.0 (105).…”

“…Glucose stimulates production and retards lysis of such suspensions. Like the complete fermentation, resting-cell synthesis is susceptible to inhibition by inorganic phosphate (75,103), although a low level such as 5 X 10-4 M stimulates production (85).…”

“…With some strains, addition of arginine and inositol to fermentation media increases streptomycin yields (35,42,72,75,86,111); streptidine has also been reported to stimulate production (86). Synthesis of streptomycin by washed suspensions may also be stimulated by arginine and inositol and by streptidine or streptobiosamine (75,85). Reported stimulation by glutamine and asparagine (106) could be due to increased transamination, although glutamine probably also plays a role in the synthesis of the N-methyl-L-glucosamine moiety.…”