The effect of DL-ethionine on fermentations of Streptomyces lincolnensis depends on the composition of the fermentation media used (complex or synthetic), the levels of ethionine added, and the time of addition of the ammoacid. Addition of ethionine into fermentations of S. lincolnensis grown in a complex medium resulted in the production of S-demethyl-S-ethyllincomycin. On the other hand, when ethionine was added into cultures of the organism grown in synthetic medium, S-demethyl-S-ethyllincomycin and a new antibiotic identified as N, S-didemethyl-N, S-diethyllincomycin were produced. The production of these two analogs of lincomycin by S. lincolnensis suggests that ethionine participates in transethylation reactions on both the nitrogen and the sulfur of the lincomycin molecule.
The incorporation of H3-lysine into Bacillus subtilis cells ceased almost immediately after the addition of siomycin, while the continued incorporation of C14-uridine and of C14-thymidine into the trichloroacetic acid-insoluble fraction of the cells was observed for at least a further 20 minutes. In bacterialcell free systems (Bacillus subtilis and Escherichia coli) siomycin inhibits polyadenylic acid directed polylysine synthesis and polyuridylic acid-directed polyphenylalanine synthesis. However, aminoacyl-transfer RNA synthesis was hardly affected. The "soluble siomycin", monothiomalic acid-siomycin A, was found to have an inhibitory action on bacterial protein biosynthesis, similar to and to roughly the same extent as siomycin A. In contrast to bacterial protein synthesis, C14-leucine incorporation into rabbit reticulocyte hemoglobin was not significantly decreased by the addition of siomycin. Protein biosynthesis in a cell-free system from rabbit reticuloeytes was also found to be highly resistant to this antibiotic. These results are in harmony with the previous observation that siomycin showed little toxicity to mammals.
New antibiotics, dienomycins A, B and C were isolated from the culture filtrate of the strain MC67-C1 by a chemical screening method using WOOD reagent. Dienomycins are derivatives of (4-phenylbutadienyl) pipecolin, Dienomycins A and B contain an alkoxyl group, and instead, C contains a hydroxyl group. Dienomycins are the first examples of mierobial metabolites having piperidine and phenylbutadiene structures. Dienomycin A is active only against mycobacteria.
The chemical structures of dienomycins A, B and C were established mainly by the studies of their NMR spectra as follows : A, 4-isobutyroyloxy-3-methyl-2-(4-phenylbutadienyl) piperidine ; B, 4-acetoxy-3-methyl-2-(4-phenylbutadienyl)piperidine ; C, 4-hydroxy-3-methyl-2-(4-phenylbutadienyl)piperidine.
A constitutive peptide antibiotic lactonase opening the lactone linkage of dihydrostaphylomycin S was isolated from Actinoplanes missouriensis. Approximately 200-fold purification was achieved by ammoniumsulfate precipitation followed by chromatography on calcium phosphate-cellulose, DEAE-cellulose, and Sephadex G-200 columns. The molecular weight, as determined by gel filtration on Sephadex G-200, is 35, 000. The Km value for dihydrostaphylomycin S is 3.73×10-4M. This enzyme also hydrolyzed the lactone bond in echinomycin, etamycin, staphylomycin S, stendomycin, and vernamycin Bα. The enzyme content of the cells was increased by addition of these peptides and also actinomycin to the growing culture.