ABSTRACT
A novel, potent and selective inhibitor of bacterial tyrosyl tRNA synthetase, designated SB-219383 has been isolated from Micromonospora sp. NCIMB 40684. The fermentation, isolation and some properties are described, whilst the structure determination is described in the succeeding paper). SB-219383 showed competitive, inhibitory activity against a Staphylococcus tyrosyl tRNA synthetase, with an IC50 of <1 nM, and exhibited weak in vitro activity against some Streptococcus sp.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/isolation & purification , Enzyme Inhibitors/isolation & purification , Furans/isolation & purification , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Chromatography, High Pressure Liquid , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Fermentation , Furans/chemistry , Furans/pharmacology , Microbial Sensitivity Tests , Micromonospora , Tyrosine-tRNA Ligase/antagonists & inhibitorsABSTRACT
Two novel inhibitors of isoleucyl tRNA synthetase designated SB-203207 and SB-203208 have been detected in the culture of a new Streptomyces species. The fermentation, isolation and some properties of the inhibitors are described.
Subject(s)
Enzyme Inhibitors/isolation & purification , Indenes/isolation & purification , Isoleucine-tRNA Ligase/antagonists & inhibitors , Sulfonamides/isolation & purification , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Fermentation , Indenes/chemistry , Indenes/pharmacology , Microbial Sensitivity Tests , Rats , Streptomyces , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/pharmacologyABSTRACT
A potent inhibitor of seryl tRNA synthetase, designated SB-217452 has been isolated from Streptomyces sp. ATCC 700974. The fermentation, isolation, structure elucidation and some properties are described. SB-217452 showed inhibitory activity against both Staphylococcus aureus and rat seryl tRNA synthetases, with similar IC50 values of approximately 8 nM. The inhibitor is the serine linked nucleoside moiety of the antibiotic albomycin delta2. In contrast to albomycin delta2, SB-217452 showed only very weak antibacterial activity against a limited range of microorganisms. The compound has not been previously reported as a naturally occurring metabolite. In addition to SB-217452, albomycin delta2 Fe3+ complex and the novel Al3+ complex were isolated from the fermentation. These complexes had no seryl tRNA synthetase inhibitory activity.
Subject(s)
Enzyme Inhibitors/pharmacology , Pyrimidinones/pharmacology , Serine-tRNA Ligase/antagonists & inhibitors , Streptomyces/chemistry , Thiophenes/pharmacology , Animals , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Pyrimidinones/chemistry , Pyrimidinones/isolation & purification , Rats , Spectrometry, Mass, Fast Atom Bombardment , Staphylococcus aureus/enzymology , Thiophenes/chemistry , Thiophenes/isolation & purificationSubject(s)
Immunosuppressive Agents , Streptomyces/metabolism , Animals , Carrier Proteins/metabolism , Cell Division/drug effects , Chemical Phenomena , Chemistry, Physical , Concanavalin A/pharmacology , DNA-Binding Proteins/metabolism , Heat-Shock Proteins/metabolism , Lipopolysaccharides/pharmacology , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Polyenes/chemistry , Polyenes/isolation & purification , Polyenes/metabolism , Polyenes/pharmacology , Pyrans/chemistry , Pyrans/isolation & purification , Pyrans/pharmacology , Recombinant Proteins/metabolism , Sirolimus , Spleen/cytology , Tacrolimus Binding ProteinsABSTRACT
The filamentous cyanobacterium Spirulina platensis has been examined for salt tolerance and osmotic adjustment. Salinities up to 150% seawater had little effect on growth yield or photosynthetic O2 evolution; higher salinities were markedly inhibitory. Osmotic adjustment was achieved by the intracellular accumulation of the low-molecular-weight carbohydrate glucosyl-glycerol in response to increased external salinity: in fullstrength (100%) seawater glucosyl-glycerol accounted for approximately 5.0% of the dry weight of the cyanobacterium. Trehalose was also present, particularly in cells at low salt concentration, and in 50% seawater medium accounted for up to 1.0% of the dry weight of the cyanobacterium. For cells grown in 100% seawater the ratio of trehalose to glucosyl-glycerol varied with temperature: at 37°C trehalose comprised 31% (w/w) of the low-molecular-weight carbohydrates while at 20°C only 9% of the total was trehalose. When subjected to hypo-osmotic shock the intracellular concentration of glucosyl-glycerol decreased and this was mirrored by an increase in glycogen. An understanding of the osmotic adjustment of S. platensis has implications both for the mass culturing of this and other strains of Spirulina and possibly also for the quality of the harvested product.
