The characteristics of streptomycete strain No. T-2636 producing antibiotics T-2636A, B, C, D, E, F and Mare given and Streptomyces rochei var. volubilis is proposed as the name for this new taxon. The antibiotics T-2636 A, B, C and D show antibacterial activity against Gram-positive bacteria and antibiotic T-2636 M shows antifungal activity. The production ratio of components A, B, C and D depends on cultural conditions. An esterase produced by the organism hydrolyzes the acetyl group of antibiotic T-2636 A converting it into antibiotic T-2636 C.
Five anti-Gram-positive bacterial components were isolated from the fermented broth of Streptomyces rochet var. volubilis and named as T-2636 A, B, C, D and E. T-2636 A, C, D and E are N-containing neutral lipophilic antibiotics and have the molecular formulae of C27H35NO8, C25H33NO7, C27H37NO8 and C26H37NO6, respectively. T-2636 B, C43H72O17, is a neutral macrolide. T-2636 Mobtained from the mycelium was assumed to be a polyene macrolide. The physico-chemical characterization of these components reveals that T-2636 B, D and E are new antibiotics and that T-2636 A, C, D and E belong to the lankacidin group. T-2636 A and C are identical with bundlin B and lankacidin, respectively.
A new antibiotic T-2636 F was isolated from three different sources, 1) the reaction mixture of T-2636 D with the esterase of Streptomyces rochei var. volubilis (No. T-2636), 2) the filtered broth of the Streptomyces strain, and 3) the bile and urine samples of rabbits, which was pre-administered T-2636 C parenterally. T-2636 F has the following chemical properties : colorless needles, m.p. 178-179°C(decomp.), imax 228 mju (EtOH), [α]24D -210° (c 1.0, DMF), molecular formula C25H35NO7-CH3OH. T-2636 F shows moderate activities against Gram-positive bacteria. The preparation of the enzyme of Streptomyces and application of the enzyme for bioassay of T-2636 antibiotics are described.
T-2636 C shows a strong in vitro antimicrobial activity against a variety of Gram-positive bacteria, Neisseria gonorrhoeae and Vibrio cholerae, while T-2636 A, D and F are relatively weak in this respect. T-2636 A and C are more active in vitro at pH 6.0 than at pH 9.0. The antibacterial in vitro activity is enhanced by decrease in bacterial inoculum size. Presence of horse serum in the mediumresults in the decreased activity. The development of resistance of the sensitive bacteria to T-2636 C is demonstrated by exposure according to the serial transfer method. In the cross resistance test using Staphylococcus aureus which had been maderesistant to T-2636 C or macrolide antibiotics in vitro, T-2636 C show a weak activity against microorganisms resistant to spiramycin and triacetyl-oleandomycin, but T-2636 C resistant S. aureus was sensitive to macrolide antibiotics. T-2636Cis effective against staphylococci, isolated from patients, at the similar concentration against the standard laboratory staphylococci. T-2636 demonstrated also bacteriostatic activity. The primary active site of T-2636 C on S. aureus is inhibition of the protein synthesis. T-2636 A and C are effective against experimental infections in mice by S. aureus and Streptococcus pyogenes, when administered intraperitoneally or orally. But T-2636 A was less effective by subcutaneous route.
A new antibiotic, azirinomycin, has been discovered in the culturejbroth of newly isolated strains of actinomycetes. It was produced by submerged culture in shaken Erlenmeyer flasks in complex organic media. Azirinomycin and its methyl ester were found to exhibit broad spectrum antibiotic activity, in vitro, against both Gram-positive and Gram-negative bacteria. Both azirinomycin and its methyl ester were toxic to mice, and failed to protect them against lethal bacterial infections.
Azirinomycin is a new antibiotic and is the first example of a natural product containing an azirine ring. It was isolated by ion-exchange and solvent extraction and is unstable, especially in concentrated form. It was identified as 3-methyl-2(2H) azirinecarboxylic acid by spectral measurements of its methyl ester and by identification of L-a-aminobutyric acid as a hydrogenation product.
The antifungal agent scopamycin A has been the subject of further chemical study. On treatment with acid it yields a 6-deoxy sugar which has been determined by nmr spectroscopy and chemical synthesis to be 2-O-methyl-L-rhamnose (6-deoxy-2-O-methyl-L-mannose).