Isolation of azalomycins F3, F4 and F5 from azalomycin F-complex crystals was successfully conducted. F3 was less soluble in methanol than other components and was isolated by fractional crystallization of F-complex from 80-100% methanol in water. F4 and F5 were separated by P-cellulose column chromatography, from which F5 and F4 were eluted with 60 % aqueous methanol and 0.01 M ammonium acetate in 60 % aqueous methanol, respectively. Determination of physico-chemical as well as biological properties pointed to a very close resemblance of the structures of these components.
The microbiological characteristics of Streptomyces strain No. 7906 include formation of white aerial mycelium, light brown growth and thick aerial hyphae forming tufts. Strain No. 7906 was compared with known species and identified as a new species and given the name Streptomyces tateyamensis. Streptomyces tateyamensis No. 7906 produces new sulfur-containing peptide antibiotics which are named thiopeptins. The major component, thiopeptin B, is obtained as a crystalline powder decomposing at 219-222°C, and exhibiting optical rotation [a]23D -80°(c 1, chloroform). Its elementary analysis suggested the empirical formula C72H90O22N18S6. The ultraviolet absorption maxima (shoulder) were found at 230-250, 295 and 305 mμ. Thiopeptin B showed strong antibacterial activity against Gram-positive bacteria and had no cross resistance with penicillins, aminoglycoside antibiotics, tetracyclines and macrolides. The administration of 500 mg/kg of this antibiotic into mice by intraperitoneal route did not result in any toxic symptom.
The absolute configuration of stendomycidine (I), a constituent of the peptide antibiotic stendomycin, was determined. Optical rotatory dispersion (ORD) measurements showed the configuration at the α-carbon atom to be that of an L-amino acid. Degradation of stendomycidine with N-bromosuccinimide yielded 2-methylimino-3-methyl-hexahydropyrimidine-4-carboxylic acid (II), a compound with only one center of asymmetry. A comparison of the ORD spectrum of compound II with that of 2-imino-hexahydropyrimidine-4-carboxylic acid (III), prepared from authentic L-α, γ-diaminobutyric acid, showed that the second center of asymmetry also has the L-configuration. Hence, the L-erythro configuration was assigned to stendomycidine. Comparison of the nmr spectra of stendomycidine and capreomycidine added some additional support to the above assignment.
A Streptomyces species, originally designated as No. 751, isolated from soil, was carefully studied from the standpoint of its morphological, physiological, and cultural characteristics. Because it produces soluble, deep purplish-red pigment in mixed culture with various microorganisms, but does not produce such pigment when cultivated independently, it is proposed as a new species and is designated Streptomyces propurpuratus nov. sp. SHINOBU et KANDA. The type strain is designated as OEU No. 751. It is not difficult to imagine that, in nature, a product of metabolism of a microorganism might be changed by the effect of a product of metabolism of another microorganism, whether the reactions are chemical or enzymatic. The authors believe that such phenomenaoccur not only with regard to pigment formation, but also with regard to production of antibiotics. An example of such a phenomenon is reported herein.
Cefazolin, 7-[l-(l H)-tetrazolylacetamido]-3-[2-(5-methyl-l, 3, 4-thiadiazolyl-thiomethyl]-Δ3-cephem-4-carboxylic acid, is a new semisynthetic antibiotic having a broad spectrum of antibacterial activity. A synthesis of cefazolin and its chemical properties are described.
Cefazolin is a new antibiotic derived from 7-aminocephalosporanic acid, having the structure of 7-[l-(lH)-tetrazolylacetamido]-3-[2-(5-methyl-l, 3, 4-thiadiazolyl)-thiomethyl]-Δ3-cephem-4-carboxylic cid. This substance is a broad-spectrum antibiotic, active in vitro against most of Gram-positive and Gram-negative species of bacteria except for Ps. aeruginosa, and is also active against penicillinase-producing strains of Staph. aureus. The activity of cefazolin against fresh isolates of E. coli and Kl. pneumoniae seems superior to those of other antibiotics used in this study. The in vitro activity of cefazolin is little influenced by size of inoculum, presence of rabbit serum, or kinds or properties of test medium. The activity of cefazolin is apparently bactericidal against both Gram-positive and Gram-negative bacteria at or above the MIC levels. In experiments on the development of resistance in vitro, the MICs of cefazolin against Staph. aureus strain 209P and E. coli strain NIHJ increase slowly in a stepwise over a period of 17 transfers. The rate of resistance development of cefazolin is comparable with that of cepholoridine or ampicillin. Cefazolin is relatively stable to enzymes from Staph. aureus and E. coli, which readily inactivate ampicillin and benzyl penicillin. Cefazolin is not remarkably degraded by the tissue homogenates of rat, although cephalothin is degraded quite rapidly. Cefazolin, in the single subcutaneous dose, shows excellent protecting activity against experimental infections in mice infected with both PC-sensitive and resistant strains of Staph. aureus, and is also fairly effective against infections in mice with Diplococcus pneumoniae, E. coli and Proteus mirabilis.
Acid hydrolysis of the peptide antibiotic amphomycinliberates a group of five basic amino acids. The major components of this mixture were isolated in pure form and identified as L, -threo-α, β-diaminobutyric acid and D-erythro-α, β-diaminobutyric acid. Both occur in the parent molecule. The basic amino acids present in minor amounts are also discussed.
A new antibiotic SF-733 inhibiting both Gram-negative and Gram-positive bacteria was isolated from Streptomyces ribosidificus nov. sp., strain SF-733. Antibiotic SF-733 obtained as colorless needles has a molecular formula C17H34N4O10, and is concluded to be a new aminoglycosidic, water-soluble and basic antibiotic based on its physical and chemical properties.