Two metabolites, active against gram-positive bacteria, have been isolated from a strain of Actinomycetales. The chemical structure of one of the two, named tetrenolin, has been previously described1). The present paper deals with the description of the producing organism, the isolation and properties of the two metabolites.
N-Demethylcelesticetin and N-demethyl-7-O-demethylcelesticetin are antibacterial agents produced by Streptomyces caelestis strain 22218 a, a mutant of S. caelestis. As in the case of celesticetin, both antibiotics are active mainly against Gram-positive organisms.
A new antibiotic, designated X-5108, produced by a new species of microorganism named Streptomyces goldiniensis var. goldiniensis, has been isolated in essentially pure but amorphous form. Assay methods, and cultivation and isolation procedures for the antibiotic are described. The antibiotic is active in vitro primarily against a number of gram-positive bacteria, whereas in vivo it is especially active against Streptococcus pyogenes infections of mice and as a poultry growth promotant. It shows a very low toxicity in mice with an LD50 of >lg/kg sbc, and >4 g/kg p.o. Its empirical formula is C44H62N2O12. Structural studies reveal one methoxyl, one N-methyl and six C-methyl groups. UV, IR and NMR spectra and optical rotation of the pure antibiotic are given. The antibiotic appears to belong to a new chemical class.
When the -S-S- compound ELLMAN'S reagent was combined either with the respiratory inhibitor antimycin or the uncoupling agent 2, 4-dinitrophenol an ATP-energized mitochondrial volume change was induced. Thus ELLMAN'S reagent behaved as an electrophilic thiol reagent analogous to showdomycin and N-ethylmaleimide. These results encouraged the search for possible reactions between the pivotal mitochondrial thiol group and biologically important substances which contain the -S-S- grouping even though older reports in the literature of the induction of mitochondrial swelling by biologically important -S-S- compounds were recently discounted.
When gliotoxin, an antibiotic, an antitumor agent and an antiviral agent, was combined with either a respiratory inhibitor or an uncoupling agent, an ATP-energized mitochondrial volume change was induced. The effect was attributed to the reaction of an exposed nucleophilic mitochondrial thiol group with the electrophilic -S-S- group in gliotoxin. While this type of interaction may be applied to assist the antitumor and toxic activities of gliotoxin it is difficult to relate the reported interaction to the antiviral activity of gliotoxin except as a model reaction.
Gliotoxin by itself induced a mitochondrial volume change believed to be respiration energized as the effect was blocked by either antimycin or 2, 4-dinitrophenol. It has been postulated that the pivotal mitochondrial thiol group interacted with the -S-S- bond in gliotoxin to form a new -S-S- bond and a new extended pivotal mitochondrial thiol group. The behaviour of gliotoxin with mitochondria was clearly differentiated from that of ELLMAN'S reagent, showdomycin and N-ethylmaleimide, and could account for the antibiotic and antitumor properties of gliotoxin and with certain qualifications the antiviral properties of gliotoxin.
From a bacterial culture a new antibiotic, O-[L-norvalyl-5]-isourea, was isolated. The structure was determined by mass spectrometry and confirmed by chemical synthesis. The antibiotic activity is inhibited by L-arginine, L-ornithine and L-citrulline.