Studies on Streptomyces Griseocarneus and the Production of Hydroxystreptomycin

Abstract

The production of streptomycin is limited mostly to a few strains of Streptomyces griseus (Schatz, Bugie, and Waksman, 1944; Waksman, Reilly, and Johnstone, 1946; Carvajal, 1946a and b) and to Streptomyces bikiniensis (Johnstone and Waksman, 1948). Trussell, Fulton, and Grant (1947) examined a strain of Streptomyces which appeared to produce both streptomycin and streptothricin. Although this organism resembled Streptomyces lavendulae, it possessed morphological and biochemical characteristics that differentiated it from the described species. More recently, Benedict et al. (1950) reported that a strain of Streptomyces griseocarneus nov. sp. produced a closely related member of the streptomycin series, hydroxystreptomycin, which differed from streptomycin only in having a hydroxymethyl group instead of a methyl group in the streptose portion of the molecule. From a strain of Streptomyces similar to, but not identical with, S. griseocarneus, Grundy et al. (1950) isolated and characterized an antibiotic identical with hydroxystreptomycin. The purpose of this paper is (1) to provide a detailed morphological and physiological description of S. griseocarneus as stipulated by Benedict et al. (1950), and (2) to report studies on the production of hydroxystreptomycin by this organism in laboratory and pilot-plant scale fermentation and to consider other factors encountered in this work. EXPERIMENTAL METHODS AND RESULTS

Comparative aspects of development and differentiation in actinomycetes.

“…The possible regulatory functions of at least some antibiotics are further exemplified by extreme sensitivity to an antibiotic at certain developmental stages. Thus, spore germination in S. griseocarneus was inhibited by 5 ug of streptomycin, whereas mycelial growth occurred in the presence of 200 to 300 ,ug of the antibiotic (40).…”

“…On dialysis against 10-2 M tris(hydroxymethyl)aminomethane buffer containing VOL. 40,1976 sisted as 7MS monomers. Both types of ribosomes were shown to be able to dissociate into 505 and 30S subunits.…”

“…Studies of heat resistance of -Streptomyces VOL. 40,1976 spores usually rely on conventional techniques involving suspensions of heated cells plated on solid nutrient media. Deviation from such techniques appeared to be instrumental in revealing the ability of such spores to regain their viability after heating.…”

“…However, its use broadens the category of VOL. 40,1976 substances to be considered almost indefinitely. Under some conditions, regulatory mutants of E. coli can probably be induced to overproduce certain amino acids and ribosides.…”

“…Possible examples of the latter situation would include "protoactinorodine" (53) and, especially, "proviridomycin" (45,349,350), a protopigment, the final color of which would depend on availability in excess of a particular (among several VOL. 40,1976 possible) ions in the medium at a certain critical period of time. Even streptomycin seems to be "adjusted" to its final and more active form as a result of wD-mannosidase action, the activity of enzyme being dependent on glucose exhaustion in the fermentation medium (102).…”