Studies on the Biosynthesis of Streptomycin

Abstract

1962. iMyo-inositol, especially in combination with arginine, enhances streptomycin production. Compounds which show structural relationship with myo-inositol are ineffective. Myo-inositol decreases the incorporation of CI4-glucose into streptomycin, particularly into streptidine. This effect suggests that myo-inositol is a precursor of the streptidine ring. Methionine stimulates antibiotic production in a synthetic medium but proves to be unfavorable in a complex medium. The y-and S-isomers of hexachlorocyclohexane inihibit streptomycin formation. The formation of streptomycin by washed mycelium was studied. Essentially the same results were here obtained as with growing cultures.

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

“…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).…”

“…The two amidino groups attached to the streptamine nitrogens are derived by transamidination from arginine. 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).…”

“…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.…”

“…As will be described below, the source of the methyl group is L-methionine. In several cases, supplementation of chemically defined media with methionine has been observed to stimulate the production of the antibiotic (42, 75); however, inhibition was noted with resting mycelia (75).…”

Variations in Strains of Streptomyces griseus Isolated from a Degenerating Streptomycin-Producing Culture

“…In the production of streptomycin, arginine and inositol were found to exert a stimulating effect (Saunders, 1950;Severina, Gorskaya, and Gracheva, 1959;Egorov, 1959;Galanina and Agatov, 1959;Majumdar and Kutzner, 1962a). NMajumdar and Kutzner (1962a) reported that these compounds stimulated streptomycin production of the same culture used by me as the original culture.…”