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Biomedical subjects

A L Demain

Publications and source records attributed to A L Demain.

208 records · Page 12Linked to original sources
PubMed1966

Production of guanosine-5'-monophosphate and inosine-5'-monophosphate by fermentation.

A biotin-requiring coryneform bacterium which produces glutamic acid was mutated to adenine dependency. The adenine-requiring strain, which excreted insoine-5'-monophosphate (IMP), was further mutated to xanthine dependency. As expected, IMP was also excreted by this mutant. The mutant strain was reverted to xanthine independence in an attempt to obtain a culture with an altered IMP dehydrogenase which would be less sensitive to feedback inhibition by guanosine-5'-monophosphate (GMP). A revertant was obtained which produced GMP and IMP, each at 0.5 g per liter. The reversion to xanthine independence had resulted in a concomitant requirement for isoleucine, leucine, and valine. Further mutation to increased nutritional requirements led to culture MB-1802, which accumulated 1 g per liter each of GMP and IMP. Both nucleotides were isolated in pure form. The concentrations of GMP and IMP produced by MB-1802 were four times that of cytidylate, uridylate, or adenylate, indicating that the mechanism of GMP and IMP production was direct and not via ribonucleic acid breakdown.

Journal Article↗
PubMed1965

Production of xanthosine-5'-monophosphate and inosine-5'-monophosphate by auxotrophic mutants of a coryneform bacterium.

Although most microorganisms with genetic blocks in the purine nucleotide sequence excrete breakdown products, a coryneform bacterium was found to accumulate intact 5'-nucleotides in the extracellular medium. Adenineless mutants accumulated 0.4 to 0.6 g of inosine-5'-monophosphate per liter of broth. The yield of this nucleotide was increased to 0.8 to 0.9 g per liter when such mutants were mutated to xanthine dependence. Induction of a specific guanine requirement in adenineless auxotrophs resulted in cultures capable of producing high yields of xanthosine-5'-monophosphate (3 to 4 g per liter). Pure xanthosine-5'-monophosphate was isolated from broth by a procedure involving ion-exchange chromatography, charcoal adsorption, and barium precipitation.

Corynebacterium↗
PubMedDate not supplied

Incorporation of acetate, propionate, and methionine into rapamycin by Streptomyces hygroscopicus.

Labelling experiments with 13C-labelled precursors demonstrated that the majority of the macrolide ring of rapamycin is formed from six acetate and seven propionate units. A two-carbon unit in the ring was not labelled by acetate, propionate, glycine, or methionine. Methionine and glycine did, however, label the three methoxy groups of rapamycin to a high degree. Results from the incorporation experiments demonstrated that there were errors in the published 13C-nmr spectral assignments for rapamycin; these have now been corrected.

Acetates↗
PubMedDate not supplied

The beta-lactam antibiotics: past, present, and future.

The discovery and development of the beta-lactam antibiotics are among the most powerful and successful achievements of modern science and technology. Since Fleming's accidental discovery of the penicillin-producing mold, seventy years of steady progress has followed, and today the beta-lactam group of compounds are the most successful example of natural product application and chemotherapy. Following on the heels of penicillin production by Penicillium chrysogenum came the discoveries of cephalosporin formation by Cephalosporium acremonium, cephamycin, clavam and carbapenem production by actinomycetes, and monocyclic beta-lactam production by actinomycetes and unicellular bacteria. Each one of these groups has yielded medically-useful products and has contributed to the reduction of pain and suffering of people throughout the world. Research on the microbiology, biochemistry, genetics and chemistry of these compounds have continued up to the present with major contributions being made by both individual and collaborative groups from industry and academia. The discovery of penicillin not only led to the era of the wonder drugs but provided the most important antibiotics available to medicine. Continued efforts have resulted in the improvement of these compounds with respect to potency, breadth of spectrum, activity against resistant pathogens, stability and pharmacokinetic properties. On the research front, major advances are being made on structural and regulatory biosynthetic genes and metabolic engineering of the pathways involved. New semisynthetic compounds especially those designed to combat resistance development are being examined in the clinic, and unusual non-antibiotic activities of these compounds are being pursued. Although seventy years of age, the beta-lactams are not yet ready for retirement.

Actinomycetales↗
PubMedDate not supplied

An overview of biotechnology.

Recombinant DNA technology, hybridoma technology, enzyme engineering, and protein engineering are all parts of the new biotechnology, which is having a major effect on research in health care, diagnostics, and agriculture, and promises to make inroads in the practices of other industries such as petroleum, mining, foods, and chemicals.

Agriculture↗
PubMedDate not supplied

Mutagenicity and antibacterial activity of mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum.

Twelve mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum in solid-state fermentation on grains were purified and tested for mutagenicity and antibacterial activity in Salmonella/mammalian microsome assays. The mutations studied were reversions of histidine auxotrophs to prototrophy in strains TA98 and TA100 and forward mutations to 8-azaguanine resistance (8AGR) in strain TM677. Rubroskyrin, (+)rugulosin, lumiluteoskyrin [a photoproduct of (-)luteoskyrin], and simatoxin [a new water-soluble metabolite of unknown structure] induced 8AGR mutations in strain TM677 but not histidine reversions in strains TA98 and TA100. Mutagenic potency was reduced by rat-liver microsomes. The carcinogens (-)luteoskyrin and cyclochlorotine were antibacterial but not mutagenic. (+)Rugulosin, rubroskyrin, lumiluteoskyrin, and high concentrations of simotoxin were also antibacterial. Antibacterial activity but not mutagenicity was observed with pibasterol and skyrin. Chrysophanol, islandicin, iridoskyrin, and emodin were inactive as mutagens or as antibacterial agents.

Animals↗