Butirosin Sulfate: A water-soluble aminoglycosidic antibiotic complex isolated from fermentation filtrates of Bacillus circulans. Two components (A and B) have been separated from the complex. Both are active against many gram-positive and some gram-negative bacteria.Ribostamycin: A broad-spectrum antimicrobial isolated from Streptomyces ribosifidicus.Framycetin: A component of NEOMYCIN that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed)Aminoglycosides: Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.Bacillus: A genus of BACILLACEAE that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic.Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.Heparitin Sulfate: A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.Kanamycin Kinase: A class of enzymes that inactivate aminocyclitol-aminoglycoside antibiotics (AMINOGLYCOSIDES) by regiospecific PHOSPHORYLATION of the 3' and/or 5' hydroxyl.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis.Hepatic Encephalopathy: A syndrome characterized by central nervous system dysfunction in association with LIVER FAILURE, including portal-systemic shunts. Clinical features include lethargy and CONFUSION (frequently progressing to COMA); ASTERIXIS; NYSTAGMUS, PATHOLOGIC; brisk oculovestibular reflexes; decorticate and decerebrate posturing; MUSCLE SPASTICITY; and bilateral extensor plantar reflexes (see REFLEX, BABINSKI). ELECTROENCEPHALOGRAPHY may demonstrate triphasic waves. (From Adams et al., Principles of Neurology, 6th ed, pp1117-20; Plum & Posner, Diagnosis of Stupor and Coma, 3rd ed, p222-5)Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Blind Loop Syndrome: A malabsorption syndrome that is associated with a blind loop in the upper SMALL INTESTINE that is characterized by the lack of peristaltic movement, stasis of INTESTINAL CONTENTS, and the overgrowth of BACTERIA. Such bacterial overgrowth interferes with BILE SALTS action, FATTY ACIDS processing, MICROVILLI integrity, and the ABSORPTION of nutrients such as VITAMIN B12 and FOLIC ACID.Breath Tests: Any tests done on exhaled air.Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.Terminology as Topic: The terms, expressions, designations, or symbols used in a particular science, discipline, or specialized subject area.Enzymes: Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.International Agencies: International organizations which provide health-related or other cooperative services.Molecular Biology: A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.International Cooperation: The interaction of persons or groups of persons representing various nations in the pursuit of a common goal or interest.alpha-Macroglobulins: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)History, 18th Century: Time period from 1701 through 1800 of the common era.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.History, 17th Century: Time period from 1601 through 1700 of the common era.Biomedical Research: Research that involves the application of the natural sciences, especially biology and physiology, to medicine.Ontario: A province of Canada lying between the provinces of Manitoba and Quebec. Its capital is Toronto. It takes its name from Lake Ontario which is said to represent the Iroquois oniatariio, beautiful lake. (From Webster's New Geographical Dictionary, 1988, p892 & Room, Brewer's Dictionary of Names, 1992, p391)Gene Library: A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Dentin-Bonding Agents: Cements that act through infiltration and polymerization within the dentinal matrix and are used for dental restoration. They can be adhesive resins themselves, adhesion-promoting monomers, or polymerization initiators that act in concert with other agents to form a dentin-bonding system.Parenteral Nutrition Solutions: Specialized solutions for PARENTERAL NUTRITION. They may contain a variety of MICRONUTRIENTS; VITAMINS; AMINO ACIDS; CARBOHYDRATES; LIPIDS; and SALTS.Research: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)Kanamycin Resistance: Nonsusceptibility of bacteria to the antibiotic KANAMYCIN, which can bind to their 70S ribosomes and cause misreading of messenger RNA.Drug Discovery: The process of finding chemicals for potential therapeutic use.Small Molecule Libraries: Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Capreomycin: Cyclic peptide antibiotic similar to VIOMYCIN. It is produced by Streptomyces capreolus.Dermatan Sulfate: A naturally occurring glycosaminoglycan found mostly in the skin and in connective tissue. It differs from CHONDROITIN SULFATE A (see CHONDROITIN SULFATES) by containing IDURONIC ACID in place of glucuronic acid, its epimer, at carbon atom 5. (from Merck, 12th ed)Absorbable Implants: Implants constructed of materials designed to be absorbed by the body without producing an immune response. They are usually composed of plastics and are frequently used in orthopedics and orthodontics.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Thiocapsa: A genus of anoxygenic, photosynthetic, nonmotile, spherical to slightly ovoid bacterial cells occurring singly, or in aggregates of two or four, and usually surrounded with slime. It is found in stagnant water, mud of ponds, estuaries, and microbial mats of salt marshes. (From Bergey's Manual of Determinative Bacteriology, 9th ed)Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours.Chromatium: A genus of gram-negative, ovoid to rod-shaped bacteria that is phototrophic. All species use ammonia as a nitrogen source. Some strains are found only in sulfide-containing freshwater habitats exposed to light while others may occur in marine, estuarine, and freshwater environments.ElastinBooksConsultants: Individuals referred to for expert or professional advice or services.Culdoscopy: Endoscopic examination, therapy or surgery of the female pelvic viscera by means of an endoscope introduced into the pelvic cavity through the posterior vaginal fornix.Drug Contamination: The presence of organisms, or any foreign material that makes a drug preparation impure.Ambroxol: A metabolite of BROMHEXINE that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride.Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect.

Purification and characterization of 2-deoxy-scyllo-inosose synthase derived from Bacillus circulans. A crucial carbocyclization enzyme in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics. (1/31)

The biosynthesis of 2-deoxystreptamine, the central aglycon of a major group of clinically important aminoglycoside antibiotics, commences with the initial carbocycle formation step from D-glucose-6-phosphate to 2-deoxy-scyllo-inosose. This crucial step is known to be catalyzed by 2-deoxy-scyllo-inosose synthase, which has not yet been characterized so far. Reported in this paper is the first purification of 2-deoxy-scyllo-inosose synthase from butirosin-producing Bacillus circulans SANK 72073 to electrophoretic homogeneity. The enzyme was isolated as a heterodimeric protein comprising from a 23 kDa- and a 42 kDa polypeptide chains. The Km of the enzyme for D-glucose-6-phosphate was estimated to be 9.0 x 10(-4) M and that for NAD+ 1.7 x 10(-4) M, kcat for D-glucose-6-phosphate being 7.3 x 10(-2) s(-1). The presence of Co2+ was essential for the enzyme activity, but Zn2+ was totally inhibitory. While the reaction mechanisms are quite similar, 2-deoxy-scyllo-inosose synthase appears to be distinct from dehydroquinate synthase in the shikimate pathway, with respect to the quaternary structure, metal ion requirement, and the kinetic parameters.  (+info)

Butirosin-biosynthetic gene cluster from Bacillus circulans. (2/31)

Butirosin is an interesting 2-deoxystreptamine (DOS)-containing aminoglycoside antibiotic produced by non-actinomycete Bacilli. Recently we were successful in purification of 2-deoxy-scyllo-inosose synthase from butirosin-producer Bacillus circulans as the key enzyme for the biosynthesis of DOS, in cloning of the responsible gene (btrC), and in its overexpression in Escherichia coli. The present study involved gene-walking approach, which allowed us to find a gene cluster around btrC. The function of each gene was further investigated by gene disruption, and the disruptants of btrB, btrC, btrD and btrM showed no antibiotic producing activity. Therefore, the gene cluster found so far was determined to be a part of the butirosin biosynthetic gene cluster. Functions of some ORFs are also discussed in terms of butirosin biosynthesis on the basis of database search.  (+info)

Significance of the 20-kDa subunit of heterodimeric 2-deoxy-scyllo-inosose synthase for the biosynthesis of butirosin antibiotics in Bacillus circulans. (3/31)

A gene (btrC2) encoding the 20-kDa subunit of 2-deoxy-scyllo-inosose (DOI) synthase, a key enzyme in the biosynthesis of 2-deoxystreptamine, was identified from the butirosin-producer Bacillus circulans by reverse genetics. The deduced amino acid sequence of BtrC2 closely resembled that of YaaE of B. subtilis, but the function of the latter has not been known to date. Instead, BtrC2 appeared to show sequence similarity to a certain extent with HisH of B. subtilis, an amidotransferase subunit of imidazole glycerol phosphate synthase. Disruption of btrC2 reduced the growth rate compared with the wild type, and simultaneously antibiotic producing activity was lost. Addition of NH4Cl to the medium complemented only the growth rate of the disruptant, and both the growth rate and antibiotic production were restored by addition of yeast extract. In addition, a heterologous co-expression system of btrC2 with btrC was constructed in Escherichia coli. The simultaneously over-expressed BtrC2 and BtrC constituted a heterodimer, the biochemical features of which resembled those of DOI synthase from B. circulans more than those of the recombinant homodimeric BtrC. Despite the similarity of BtrC2 to HisH the heterodimer showed neither aminotransfer nor amidotransfer activity for 2-deoxy-scyllo-inosose as a substrate. All the observations suggest that BtrC2 is involved not only in the secondary metabolism, but also in the primary metabolism in B. circulans. The function of BtrC2 in the butirosin biosynthesis appears to be indirect, and may be involved in stabilization of DOI synthase and in regulation of its enzyme activity.  (+info)

Identification of L-glutamine: 2-deoxy-scyllo-inosose aminotransferase required for the biosynthesis of butirosin in Bacillus circulans. (4/31)

Using inverse PCR, two new genes (btrN and btrS) were identified upstream of the putative glycosyltransferase gene btrM in the butirosin-biosynthetic btr gene cluster of Bacillus circulans. The upstream gene btrS showed significant homology with stsC of Streptomyces griseus, which encodes L-glutamine:scyllo-inosose aminotransferase in the biosynthesis of streptomycin. The function of BtrS was further confirmed by heterologous expression in Escherichia coli and chemical identification of the conversion of 2-deoxy-scyllo-inosose into 2-deoxy-scyllo-inosamine. The identification of BtrS as L-glutamine:2-deoxy-scyllo-inosose aminotransferase is the first report of the aminotransferase gene responsible for 2-deoxystreptamine biosynthesis.  (+info)

New antibiotic produced by bacteria, 5-beta-D-xylofuranosylneamine. (5/31)

A new aminoglycoside antibiotic was isolated from the fermentation broths of two strains of Bacillus species. The antibiotic is active against gram-positive and some gram-negative bacteria, and its antimicrobial spectrum is similar to that of ribostamycin. The chemical structure was determined to be 5-beta-d-xylofuranosylneamine, which is identical to the deacylated product obtained from butirosin A.  (+info)

Butirosin compared with gentamicin in vitro and in vivo. (6/31)

Butirosin (BTN) (P. W. K. Woo, G. L. Coffey, H. W. Dion, S. A. Fusari, and G. D. Senos, U. S. Patent 3,541,078, 1970) is a new aminoglycoside antibiotic notably active against opportunist bacterial species within Pseudomonas, Klebsiella, Enterobacter, Serratia, and Proteus. Numerous comparative tests were carried out with BTN and gentamicin (GTM) in vitro and in experimental infections in mice. BTN was more active in Mueller-Hinton broth than in agar, but its activity was lessened at acid pH or under anaerobiosis, as has been observed with other aminoglycosides. In standard agar diffusion tests, inhibition zones greater than 12 mm around 30-mug BTN disks generally denoted susceptibility, equivalent to minimal inhibitory concentrations [Formula: see text] 25 mug/ml. Cross-resistance between BTN and GTM occurred in a variable manner, with a number of bacterial strains strongly resistant to GTM being moderately susceptible to BTN. In mice, after a single subcutaneous injection, absorption of both antibiotics was rapid, with peak serum levels occurring in 15 min; this was followed by rapid elimination with estimated serum half-lives of about 20 min for each. After peroral administration of high doses in mice, there was no appreciable absorption of BTN. Several tests were carried out to compare BTN and GTM with respect to minimal inhibitory concentrations in vitro, acute subcutaneous median mouse protective doses, peak serum levels at such doses, and the therapeutic ratios derived from acute median protective and lethal doses. Although GTM usually proved to be more potent antibacterially on a weight basis, observations on BTN indicated a superior effectiveness in terms of therapeutic ratios.  (+info)

Biosynthesis of the unique amino acid side chain of butirosin: possible protective-group chemistry in an acyl carrier protein-mediated pathway. (7/31)

Butirosins A and B are naturally occurring aminoglycoside antibiotics that have a (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. Semisynthetic addition of AHBA to clinically valuable aminoglycoside antibiotics has been shown both to improve their pharmacological properties and to prevent their deactivation by a number of aminoglycoside-modifying enzymes involved in bacterial resistance. We report here that the biosynthesis of AHBA from L-glutamate, encoded within a previously identified butirosin biosynthetic gene cluster, proceeds via intermediates tethered to a specific acyl carrier protein (ACP). Five components of the pathway have been purified and characterized, including the ACP (BtrI), an ATP-dependent ligase (BtrJ), a pyridoxal phosphate-dependent decarboxylase (BtrK), and a two-component flavin-dependent monooxygenase system (BtrO and the previously unreported BtrV). The proposed biosynthetic pathway includes a gamma-glutamylation of an ACP-derived gamma-aminobutyrate intermediate, possibly a rare example of protective group chemistry in biosynthesis.  (+info)

The ribostamycin biosynthetic gene cluster in Streptomyces ribosidificus: comparison with butirosin biosynthesis. (8/31)

A cluster of genes for ribostamycin (Rbm) biosynthesis was isolated from Streptomyces ribosidificus ATCC 21294. Sequencing of 31.892 kb of the genomic DNA of S. ribosidificus revealed 26 open reading frames (ORFs) encoding putative Rbm biosynthetic genes as well as resistance and other genes. One of ten putative Rbm biosynthetic genes, rbmA, was expressed in S. lividans TK24, and shown to encode 2-deoxy-scyllo-inosose (DOI) synthase. Acetylation of various aminoglycoside-aminocyclitol (AmAcs) by RbmI confirmed it to be an aminoglycoside 3-N-acetyltransferase. Comparison of the genetic control of ribostamycin and butirosin biosynthesis pointed to a common biosynthetic route for these compounds, despite the considerable differences between them in genetic organization.  (+info)