O-Carbamyl-D-serine, NH2-CO-O-CH2-CH(NH2)-COOH, was first isolated from a Streptomyces by Hagemann et al.1) Skinner et al.2) synthesized the L-isomer, which was reported to inhibit purine biosynthesis as a L-glutamine antagonist. An antibiotic, which showed stronger inhibition on a synthetic medium against B. subtilis than on a nutrient agar, was isolated from a strain closely related to Streptomyces fragilis by Okami et al,3) and was confirmed to be O-carbamyl-D-serine. They obtained this substance in a screening studies for antibiotics having an inhibitory activity against a mutant of B. subtilis requiring adenine, cytosine and uracil.
O-Carbamyl-D-serine was obtained in our laboratory from culture filtrates of a certain strains of Streptomycetes in the course of screening for D-alanine antagonists. Further studies revealed that this antibiotic selectively inhibits the biosynthesis of bacterial cell walls as described with penicillin, D-4-amino-3-isoxazolidone, vancomycin, bacitracin and novobiocin. A review of studies with these antibiotics was recently published by Perkins5). The molecular model of O-carbamyl-D-serine indicated a stereochemical structure, related to D-alanine or D-4-amino-3-isoxazolidone. Investigations of the synergistic activity with other antibiotics and mouse protection tests against Staph. Aureus by O-carbamyl-D-serine were also carried out. The results are presented in this publication.
It was reported by Anand and Davis1) that chloramphenicol prevents killing of E.coli by streptomycin when the two antibiotics are added to the bacterial culture concomitantly. Anand, Davis and Armitage2) demonstrated that chloramphenicol blocks accumulation of 14C-streptomycin in bacteria. Hurwitz and Rosano3) assumed the prerequisite of a streptomycin-induced chloramphenicol-sensitive protein synthesis for the lethal action of streptomycin. They4) also observed that chloramphenicol inhibits intrabacterial accumulation of 14C-streptomycin and suggested that streptomycin-induced protein may be a specific transport system (permease).
However, if the above assumption is correct, the induced protein synthesis appears not to be inhibited by streptomycin itself, although the antibiotic is known to interfere with protein synthesis under a certain conditions. We5) are interested in the mode of action of kanamycin and like to know whether a similar phenomenon occurs with the lethal action of kanamycin. For the purpose of elucidating these problems, the effects of antibiotics, which inhibit bacterial protein synthesis, on the lethal action of kanamycin and streptomycin were studied and the results are presented in this publication.
The antibiotics used include chloramphenicol, erythromycin, mikamycin A, puromycin, blasticidin S and tetracycline. The bactericidal action of both streptomycin and kanamycin was blocked by chloramphenicol, erythromycin, mikamycin A, blasticidin S and tetracycline, but not by puromycin.
Cervicarcin discovered in our laboratory is a new antitumor antibiotic produced by Streptomyces ogaensis. The taxonomic studies1), the physico-chemical properties2),3) and some of the chemistry4), of the agent have been already reported. This paper deals with the effect of cervicarcin and its derivatives against some of transplantable mouse tumors. The derivatives tested were as follows : cervicarcin methyl ether, tetraacetyl cervicarcin, cervicarcin glycol, cervicarcin chlorohydrin, cervicarcin chlorohydrin methyl ether and tetraacetyl cervicarcin methyl ether.
While the number of new antibiotics of streptomyces-origin has continued to increase in these years, those from fungi and bacteria became less frequent. The reason may be that the useful antibiotics were isolated from streptomyces more often than from bacteria and fungi, and streptomyces seems to be a better source of antibiotics. Griseofulvin2) and variotin3) isolated from fungi were recently shown to be efficient antibiotics, but no antibiotic isolated from Fungi imperfecti. We isolated a strain of Fungi imperfecti recently from the air, and this strain exhibited an antimicrobial activity. An active substance isolated from the fermentation filtrate was proved to be a new antibiotic and was given a name of cerulenin1). This antibiotic is heat-stable, low toxic, and showed activities against fungi and bacteria.
A detailed examination of this strain showed it to be a new species of genus Cephalosporium, and was given a name of Cephalosporium caerulens.
Cerulenin is a new antibiotic obtained from a strain of Cephalosporium caerulens,1,2) a new species of genus Cephalosporium, Fungi imperfecti. This antibiotic exhibited a strong antibacterial activity against several kinds of bacteria and a variety of fungi in vitro3). This paper deals with the fermentative production of cerulenin.