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Biomedical subjects

A L Demain

Publications and source records attributed to A L Demain.

At least 181 records · Page 10Linked to original sources
PubMed1975

Mutational biosynthesis of a new antibiotic, streptomutin A, by an idiotroph of Streptomyces griseus.

Microorganisms producing antibiotics have been genetically converted by earlier workers to mutants which cannot produce antibiotic without supplementation with a moiety of the antibiotic. These antibiotics include neomycin, kanamycin, paromomycin, butirosin, sisomicin, ribostamycin and novobiocin. Success has not been reported for organisms producing guanidinocyclitol antibiotics such as streptomycin. We mutagenized conidia of the streptomycin-producing Streptomyces griseus strain 7-455F3 with nitrosoguanidine at pH 7.0. Non-producers of streptomycin were visually selected by the agar-plug technique using Bacillus subtilis. We successfully isolated mutant MIT-A5 which produces no streptomycin unless streptidine is added to the agar medium. The streptidine-dependent phenotype was confirmed in submerged culture in flasks. Attempts to produce new antibiotics by feeding aminocyclitols to mutant MIT-A5 failed. However a new antibiotic (streptomutin A) was produced by supplementation with the guanidinocyclitol, 2-deoxystreptidine. We propose the term "mutational biosynthesis" for the production of new metabolites by the use of mutants blocked in the biosynthetic pathway to the secondary metabolite. We further propose the term "idiotroph" to properly describe such mutants.

Anti-Bacterial Agents↗
PubMed1975

Stimulation of cephalosporin production by methionine peptides in a mutant blocked in reverse transsulfuration.

The previously reported inability of methionine to stimulate cephalosporin C production in a cysteine auxotroph is due to cysteine interference with methionine uptake. In such a cse, "illicit transport" of alanylmethionine can be used to demonstrate the efficacy of methionine in such mutants blocked in the path from methionine to cysteine. This result supports the hypothesis that the stimulatory activity of methionine is not due to its ability to donate sulfur to the caphalosporin C molecule.

Acremonium↗
PubMed1974

Insensitivity of homocitrate synthase in extracts of Penicillium chyrosogenum to feedback inhibition by lysine.

We previously reported that lysine inhibits in vivo homocitrate synthesis in the lysine bradytroph, Penicillium chrysogenum L(1), and that such feedback inhibition could explain the known lysine inhibition of penicillin formation. In the present study, it was found that dialyzed cell-free extracts of mutant L(1) converted [1-(14)C]acetate to homocitrate. This homocitrate synthase activity was extremely labile but could be stabilized by high salt concentrations. The pH optimum of the reaction was 6.9, and the K(m) was 5.5 mM with respect to alpha-ketoglutarate. The reaction was also dependent upon the presence of Mg(2+), adenosine 5'-triphosphate, and coenzyme A. Surprisingly, the activity in these crude extracts was not inhibited by lysine. Benzylpenicillin at a high concentration (20 mM) partially inhibited the enzyme, an effect that was enhanced by lysine. Casein hydrolysate also partially inhibited the enzyme.

Acetates↗
PubMed1972

Fermentation process for double-stranded ribonucleic acid, an interferon inducer.

Double-stranded ribonucleic acid (ds-RNA) isolated from Escherichia coli infected with bacteriophage MS2 is a potent interferon inducer. High levels of ds-RNA are formed in nonpermissive cells infected with MU9, an amber coat protein mutant of MS2. This mutant has been used to develop a process for large-scale ds-RNA production. Preparation of quantities of MU9 lysate sufficient for ds-RNA production in fermentors is described. Over 300 mug of ds-RNA/ml can be accumulated after MU9 infection of cultures grown to high density in corn steep liquor medium. This is approximately 300 times the amount of ds-RNA made by MS2 infection of cells grown in tryptone medium. Maximum ds-RNA formation requires only 3 hr. The ds-RNA is stable and remains inside nonaerated cells for at least 17 hr.

Air↗
PubMed1972

Production of an autoinhibitor by a thermophilic bacillus.

Premature cessation of rapid, exponential growth and a low final cell yield were observed with a thermophilic bacillus in a glucose-mineral salts-vitamin medium. Restricted growth was not due to nutrient or oxygen limitation, to depressed pH, or to the physical effects of "crowding." Glucose conversion to cellular material was efficient at a low glucose charge (0.1%), but decreased with increasing concentrations of glucose. The likelihood that an autoinhibitor(s) was being produced was considered. Further studies revealed that an autoinhibitor appeared in the culture supernatant fluid at the end of the exponential phase. The factor was soluble in 75% ethanol which precipitated a large amount of extracellular slime. The crude inhibitor in the alcohol filtrate was dialyzable and withstood 3 hr of incubation at pH 2 or 12, and 30 min of boiling.

Anti-Bacterial Agents↗
PubMed1971

Microbial epoxidation of cis-propenylphosphonic to (-)-cis-1,2-epoxypropylphosphonic acid.

Eighteen species of Penicillium, one of Oidium and one of Paecilomyces were found to effect a stereospecific conversion of cis-propenylphosphonate to fosfomycin which was identified by paper chromatography and gas-liquid chromatography (GLC) of the trimethylsilyl esters. Penicillium spinulosum carried out the epoxidation only after the glucose substrate had been utilized. Glucose controlled the epoxidation since its residual concentrations in the broth severely depresses the reaction. At optimum levels of glucose, an epoxidation efficiency approaching 90% of olefin charged (0.2 g/liter) was obtained after 10 days of incubation. The olefin concentration could be increased to 0.5 g/liter when glucose was replaced by glycerol, whereby a 90% conversion to fosfomycin was attainable in 6 days. The high conversion efficiency, a good agreement between the GLC assay and bioactivity, are indicative of the levorotatory nature of the product.

Alkenes↗