Streptothricin isolation

The actinomycetes (order Actinomycetales) are nonmotile organisms that may be considered as intermediate forms between bacteria and molds. They occur abundantly in soils, composts, river and lake bottoms, in dust particles, and upon plant surfaces. The order is divided into three families comprising a number of genera. These genera are represented in nature by many thousands of species, of which several hundred have been scientifically characterized. Recent interest in the antibiotics elaborated by the actinomycetes first centered on the substance streptothricin, isolated from Streptomyces lavendulae (formerly named Actinomyces lavendulae). When this antibiotic was found to exhibit dangerous delayed toxicity effects, attention was turned to streptomycin, which had been isolated from the culture medium of a related organism. 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

First among the aminoglycosides was streptomycin, one of several antibiotics isolated from Streptomyces species by Selman Waksman—this from S. griseus in 1944. Waksman proved to be an enormously effective seeker of antibiotics in natural products. In addition to streptomycin, he discovered neomycin, another widely used antibiotic. Less important discoveries include actinomycin, clavacin, streptothricin, grisein, fradicin, and candidin. Waksman received the Nobel Prize in Physiology or Medicine in 1952. 

Waksman and his collaborators grew a batch of a soil microorganism called Actinomyces griseus and isolated their first antibiotic from the brew in 1940. They called it actinomycin, after the species of microorganism from which it was isolated. In 1942 they isolated streptothricin. Like actinomycin, it was too toxic to use in humans, but unlike actinomycin, it destroyed the tubercle bacillus. Encouraged by these discoveries, Waksman continued to test, or screen, other soil microbes for their ability to produce antibiotics with activity against the bacteria that caused tuberculosis (now known as Mycobacterium tuberculosis). 

In this section, natural products with guanidines are studied. A large group of these products consist of cyclic depsipeptides and polypeptides with arginine as an amino acid residue, produced by mainly actinomycete and cyanobacteria in some cases (ex. microcystin-LR, noduralin) [39]. Isolation of aminoglycosides (streptomycins, streptothricins [40] and their... 

Streptothricins. A mixture of antibiotics of the nucleoside type first isolated in 1942 by Waksman and Woodruff from streptomycetes. S. were first considered to be a uniform substance and given the name S. F. The mixture was later found to consist of several, frequently occurring compounds that differ in the number of /3-lysine units in the side chain. 

C17H29N7O8 459.458 Streptothricin-type antibiotic. Isol. from Streptomyces griseodiromogenes and Streptomyces sp. No. 6241. Possesses weak antimicrobial activity and shows herbicidal props. Powder. 

Streptothricin is a basic peptide, whose formula is C2oHg409Ng (581). It is antibiotic for diverse Gram-positive, Gram-negative, and acid-resistant bacteria (610), and is produced by certain strains of Streptomyces lavendulae (615). The isolation of streptothricin is as follows (455) charcoal adsorption, elution with dilute formic acid, precipitation by picric acid, and conversion of the picrate to hydrochloride, which is then purified by chromatography on either alumina or a mixture of Darco G 60 and paper pulp. The hydrochloride is converted to the crystalline helianthate which possesses a rotatory power Md = — 51.3° (c = 1.4in water). Other salts of streptothricin have been prepared, namely the reineckate (207), picrolonate, flavianate, dipicrate, and sulfate (555,581). According to... 

The nature of the neomycins — water soluble, amorphous, difficultly separable mixtures — has made their comparison to antibiotics isolated from other cultures difficult. For this reason a number of compounds isolated and reported separately have been shown subsequently to be identical to neomycin. In some cases this was accomplished by comparison of antimicrobial spectrum and paper chromatographic behavior, in others it was necessary to isolate and compare degradation products. Those antibiotics reported to be identical to the neomycins have been reviewed (Rinehart, 1964) and include streptothricins B I and B II, dextro-mycin, framycetin, flavomycin and mycifradin. Other antibiotics — fradiomycin, cohmycin — have not been estabhshed as identical, but their reported properties are so similar to those of the neomycins as to leave Httle doubt of their identity. 

---