PubMed · 2314045
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
D Blumenberg. [Erythromycin].. https://pubmed.ncbi.nlm.nih.gov/2314045/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
DEBS 1 + TE is a recombinant modular polyketide synthase (PKS) in which the first two biosynthetic modules of the 6-deoxyerythronolide B synthase are linked to the thioesterase domain normally found at the C-terminus of DEBS 3. Incubation of DEBS 1 + TE with propionyl-CoA, methylamalonyl-CoA, and NADPH gives the triketide lactone (2R,3S,4S,5R)-2,4-dimethyl-3, 5-dihydroxy-n-heptanoic acid delta-lactone (2), the cyclized form of the normal triketide chain elongation product of DEBS 1. In order to probe the molecular recognition features of the PKS and to explore its synthetic versatility, [2,3-13C2]-(2S,3R)-2-methyl-3-hydroxypentanoyl-NAC thioester (3), an analogue of the normal diketide chain elongation intermediate, and (2RS)-methyl-malonyl-CoA were incubated with DEBS 1 + TE, leading to the formation of the predicted labeled triketide ketolactone [4,5-13C2]-8, as established by 13C NMR analysis and comparison with spectra of synthetic 8. This stereoselective conversion illustrates the potential of using modular PKSs as multifunctional catalysts for the enzymatic synthesis of novel polyketides.
The oleandomycin (OM) producer, Streptomyces antibioticus, possesses a mechanism involving two enzymes for the intracellular inactivation and extracellular reactivation of the antibiotic. Inactivation takes place by transfer of a glucose molecule from a donor (UDP-glucose) to OM, a process catalyzed by an intracellular glucosyltransferase. Glucosyltransferase activity is detectable in cell-free extracts concurrent with biosynthesis of OM. The enzyme has been purified 1,097-fold as a monomer, with a molecular mass of 57.1 kDa by a four-step procedure using three chromatographic columns. The reaction operates via a compulsory-order mechanism. This has been shown by steady-state kinetic studies using either OM or an alternative substrate (rosaramycin) and dead-end inhibitors, and isotopic exchange reactions at equilibrium. OM binds first to the enzyme, followed by UDP-glucose. A ternary complex is thus formed prior to transfer of glucose. UDP is then released, followed by the glycosylated oleandomycin (GS-OM).
BACKGROUND: Neonatal conjunctivitis (ophthalmia neonatorum) continues to cause blindness because the agents used prophylactically to prevent this condition are not completely effective and are not widely available in many parts of the world. Povidone-iodine ophthalmic solution is an effective antibacterial agent with broad antibacterial and antiviral activity to which no bacteria are known to be resistant, and it is far less expensive and less toxic than the agents currently used to prevent neonatal conjunctivitis. METHODS: We conducted a masked, prospective trial involving 3117 infants born over a period of 30 months in a hospital in Kenya. Shortly after birth each infant received a 2.5 percent solution of povidone-iodine (n = 1076), a 1 percent solution of silver nitrate (n = 929), or 0.5 percent erythromycin ointment (n = 1112) in both eyes. Randomization was achieved by rotating the three medications after each was used for a week. RESULTS: Of the neonates treated with povidone-iodine, 13.1 percent had infectious conjunctivitis, as compared with 17.5 percent of those treated with silver nitrate (P < 0.001) and 15.2 percent of those treated with erythromycin (P = 0.01). Povidone-iodine was more effective against Chlamydia trachomatis than was silver nitrate (P < 0.001) or erythromycin (P = 0.008). There were 104 cases of noninfectious conjunctivitis (9.7 percent) in the povidone-iodine group, as compared with 129 in the silver nitrate group (13.9 percent, P < 0.001) and 148 in the erythromycin group (13.3 percent, P = 0.004). Many cases of noninfectious conjunctivitis were probably due to a toxic reaction to the treatment itself. The incidence of Neisseria gonorrhoeae and Staphylococcus aureus infections was similar in the three groups. CONCLUSIONS: A 2.5 percent ophthalmic solution of povidone-iodine as prophylaxis against ophthalmia neonatorum is more effective than treatment with silver nitrate or erythromycin, and it is less toxic and costs less.