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At least 19 recordsLinked to original sources
PubMed1977

Carbomycin resistance in mouse L cells.

A mutant has been isolated from the mouse cell line LM(TK-) which is stably resistant to the macrolide antibiotic, carbomycin. Mitochondrial protein synthesis in this mutant was carbomycin resistant and chloramphenicol sensitive. Fusions between carbomycin-resistant and -sensitive cells produced hybrids, most of which were sensitive to 10 microgram/ml carbomycin. At 7.5 microgram carbomycin/ml, the average population resistance is low initially but increases with time. Carbomycin-resistant cells were enucleated and fused with carbomycin-sensitive cells under a variety of selective regimes designed to allow growth of carbomycin-resistant cytoplasmic hybrids (cybrids). No transfer of carbomycin resistance via the cytoplasm was detected. Karyoplasts from carbomycin-resistant cells showed a low transfer of resistance to 7.5 microgram carbomycin/ml in karyoplast-cell fusions. Carbomycin resistance in this mutant is therefore most likely encoded in a nuclear gene.

Cell Nucleus↗
PubMed1980

Carbomycin, a macrolide antibiotic.

Carbomycin is produced by Streptomyces halstedii. It was produced in a medium containing the following ingredients (g/l): soybean meal, 30.0; glucose, 22.0; NaCl, 1.0; CaCO3, 5.0; CoCl2 . 6 H2O, 0.005; and lard oil, 4.0. Influence of trace elements on the biosynthesis of carbomycin was recorded. Methods of extraction and purification were given in the review article. Chemical and physical properties of carbomycin were also described. A microbiological assay method for carbomycin determination was described. Biosynthesis of carbomycin was reported. Mechanism of action of carbomycin on micro-organisms was also given in the review article.

Bacteria↗
PubMed1984

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. I. Microbial deepoxidation and subsequent isomerization of deltamycins A1, A2, A3, A4 (carbomycin A) and X.

Carbomycin A (deltamycin A4) was deepoxidized to carbomycin A P1 by Streptomyces halstedii subsp. deltae (a deltamycins producer), favorably under anaerobic conditions. Carbomycin A P1 was spontaneously converted to geometric isomers designated carbomycins A P2 and A P3. This type of deepoxidation and subsequent isomerization was not limited to carbomycin A, but generally occurrable in other 16-membered epoxyenone macrolide compounds. Many bacteria and actinomycetes were also found to have an ability to deepoxidize deltamycins reductively. The chemical structures of carbomycins A P1, A P2 and A P3 were elucidated as shown in Fig. 3.

Bacteria↗
PubMed1995

Nucleotide sequence analysis of the carbomycin biosynthetic genes including the 3-O-acyltransferase gene from Streptomyces thermotolerans.

A 3.2-kb DNA fragment of the carbomycin biosynthetic region including the 3-O-acyltransferase gene (acyA) from Streptomyces thermotolerans was sequenced, and four ORFs were found in the fragment. The second ORF, designated ORF-A, was transcribed in the opposite direction to the other three ORFs. The first ORF was identified as carA, a gene for carbomycin resistance. The amino acid sequence of ORF-A was homologous to proteins of the cytochrome P-450 family. Streptomyces lividans transformed with pCB20, in which ORF-A was subcloned, epoxidized carbomycin B at its C-12, 13 positions, thus producing carbomycin A. The third ORF, the amino acid sequence of which showed a homology to macrolide antibiotics O-acyltransferases was identified as acyA. The last ORF (ORF-B), which starts just 3 bp downstream from the TGA termination codon of acyA, was thought to be a carbomycin 4-O-methyltransferase gene, because the amino acid sequence deduced from ORF-B showed high homology to a putative midecamycin 4-O-methyltransferase encoded on mdmC.

Acetyltransferases↗
PubMed2000

Inhibition of the ribosomal peptidyl transferase reaction by the mycarose moiety of the antibiotics carbomycin, spiramycin and tylosin.

Many antibiotics, including the macrolides, inhibit protein synthesis by binding to ribosomes. Only some of the macrolides affect the peptidyl transferase reaction. The 16-member ring macrolide antibiotics carbomycin, spiramycin, and tylosin inhibit peptidyl transferase. All these have a disaccharide at position 5 in the lactone ring with a mycarose moiety. We have investigated the functional role of this mycarose moiety. The 14-member ring macrolide erythromycin and the 16-member ring macrolides desmycosin and chalcomycin do not inhibit the peptidyl transferase reaction. These drugs have a monosaccharide at position 5 in the lactone ring. The presence of mycarose was correlated with inhibition of peptidyl transferase, footprints on 23 S rRNA and whether the macrolide can compete with binding of hygromycin A to the ribosome. The binding sites of the macrolides to Escherichia coli ribosomes were investigated by chemical probing of domains II and V of 23 S rRNA. The common binding site is around position A2058, while effects on U2506 depend on the presence of the mycarose sugar. Also, protection at position A752 indicates that a mycinose moiety at position 14 in 16-member ring macrolides interact with hairpin 35 in domain II. Competitive footprinting of ribosomal binding of hygromycin A and macrolides showed that tylosin and spiramycin reduce the hygromycin A protections of nucleotides in 23 S rRNA and that carbomycin abolishes its binding. In contrast, the macrolides that do not inhibit the peptidyl transferase reaction bind to the ribosomes concurrently with hygromycin A. Data are presented to argue that a disaccharide at position 5 in the lactone ring of macrolides is essential for inhibition of peptide bond formation and that the mycarose moiety is placed near the conserved U2506 in the central loop region of domain V 23 S rRNA.

Anti-Bacterial Agents↗
PubMed1987

Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA.

Using dimethyl sulfate and kethoxal, we have probed antibiotic-ribosome complexes, and identified sites of interaction of chloramphenicol, erythromycin, carbomycin, vernamycin B and viomycin with 23S rRNA. Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping nonequivalent sites in the central loop of domain V. From the known functional effects of these drugs and their protection patterns, we infer that peptidyl transferase is inhibited as a result of binding antibiotics proximal to A-2451, whereas antibiotics bound proximal to A-2058 interfere with growth of the nascent polypeptide chain. Vernamycin B also strongly protects A-752, implying that this region of domain II is proximal to the central loop of domain V. Viomycin, which affects translocation and subunit dissociation, protects U-913 and G-914.

Acyltransferases↗
PubMed1982

Erythromycin, carbomycin, and spiramycin inhibit protein synthesis by stimulating the dissociation of peptidyl-tRNA from ribosomes.

In mutant Escherichia coli with temperature-sensitive peptidyl-tRNA hydrolase (aminoacyl-tRNA hydrolase; EC 3.1.1.29), peptidyl-tRNA accumulates at the nonpermissive temperature (40 degrees C), and the cells die. These consequences of high temperature were enhanced if the cells were first treated with erythromycin, carbomycin, or spiramycin at doses sufficient to inhibit protein synthesis in wild-type cells but not sufficient to kill either mutant or wild-type cells at the permissive temperature (30 degrees C). Since peptidyl-tRNA hydrolase in he mutant cells is inactivated rapidly and irreversibly at 40 degrees C, the enhanced accumulation of peptidyl-tRNA and killing were the result of enhanced dissociation, stimulated by the antibiotics, of peptidyl-tRNA from ribosomes. The implications of these findings for inhibition of cell growth and protein synthesis are discussed. Certain alternative interpretations are shown to be inconsistent with the relevant data. Previous conflicting observations on the effects of macrolide antibiotics are explained in terms of our observations. We conclude that erythromycin, carbomycin, and spiramycin (and probably all macrolides) have as a primary mechanism of action the stimulation of dissociation of peptidyl-tRNA from ribosomes, probably during translocation.

Anti-Bacterial Agents↗
PubMed1984

Deepoxidation of 16-membered epoxyenone macrolide antibiotics. III. In vitro and in vivo evaluation of deepoxidation products of carbomycin A, deltamycin A1, 4"-phenylacetyldeltamycin, angolamycin and rosamicin.

Deepoxidation products P1, P2 and P3 of carbomycin A, deltamycin A1 and 4"-phenylacetyldeltamycin showed high in vitro antibacterial and antimycoplasmal activities which were comparable to those of the respective parent compounds. By contrast, the in vitro antimicrobial potencies of angolamycin P1 and rosamicin P1 were about ten-fold lower than those of the parent macrolides. In mice, the increase in the plasma levels of the epoxyenone macrolides due to deepoxidation was highly significant with the P1, P2 and P3 derivatives of carbomycin A and 4"-phenylacetyldeltamycin, whereas angolamycin P1 gave a moderately-improved plasma level compared with angolamycin.

Animals↗
PubMed1987

Cloning and nucleotide sequence of a carbomycin-resistance gene from Streptomyces thermotolerans.

Two plasmids (pOJ158 and pOJ159) containing DNA fragments from the carbomycin(Cb)-producing strain Streptomyces thermotolerans were identified in Streptomyces griseofuscus based on their ability to confer resistance to Cb. The Cb-resistance determinants on pOJ158 and pOJ159 were designated carA and carB, respectively. In S. griseofuscus, pOJ159 also confers resistance to spiramycin, rosaramicin, lincomycin, and vernamycin B, but not to tylosin; in Streptomyces lividans, pOJ159 additionally confers resistance to erythromycin and oleandomycin. The carB gene was localized on pOJ159 to a 1.25-kb region whose nucleotide sequence was determined. The sequence has a G + C content of 68% and contains the coding sequence for carB and portions of the 5' and 3' untranslated regions. A comparison of the amino acid sequence of the protein encoded by carB (as deduced from the nucleotide sequence) with the deduced amino acid sequence of the RNA methylase from Streptomyces erythraeus (encoded by ermE) revealed extensive homology, suggesting that carB also encodes an RNA methylase. The region 5' to the coding sequence does not contain a small ORF or regions of complementarity that are commonly associated with translationally regulated macrolide-lincosamide-streptogramin B resistance genes. The 3' untranslated region contains an inverted repeat sequence that potentially can form a stable RNA stem-loop structure with a calculated delta G of -70 kcal.

Base Composition↗
PubMed1989

Production of a hybrid macrolide antibiotic in Streptomyces ambofaciens and Streptomyces lividans by introduction of a cloned carbomycin biosynthetic gene from Streptomyces thermotolerans.

The structurally related macrolide antibiotics carbomycin (Cb) and spiramycin (Sp) are produced by Streptomyces thermotolerans and Streptomyces ambofaciens, respectively. Both antibiotics contain 16-membered lactone rings to which deoxysugars are attached. There are three sugars in Sp (forosamine, mycaminose and mycarose) and two sugars in Cb (mycaminose and a derivative of mycarose containing an isovaleryl group at position 4). We have identified the gene from S. thermotolerans (designated carE), which appears to encode an enzyme that acylates this mycarose sugar, and have shown that recombinant strains containing carE can use Sp as a substrate and convert it to the hybrid antibiotic, isovaleryl Sp (ivSp). Expression of carE was demonstrated in two heterologous hosts: in S. ambofaciens, where endogenously synthesized Sp was converted to ivSp, and in Streptomyces lividans where exogenously added Sp was converted to ivSp. The carE gene was isolated on a cosmid that also encodes genes required for Cb-lactone formation. These genes reside on a DNA segment of about 70 kb and are part of a Cb biosynthetic gene cluster that is flanked by two Cb-resistance genes, carA and carB. Mapping studies and nucleotide sequence analysis revealed that carE is located at one end of this gene cluster, immediately adjacent to the carB gene. Genes carB and carE are transcribed convergently and may share a common transcriptional terminator sequence.

Acyltransferases↗
PubMed1990

Methylation of 23S ribosomal RNA due to carB, an antibiotic-resistance determinant from the carbomycin producer, Streptomyces thermotolerans.

A resistance gene, carB, originally isolated from the carbomycin-producing organism, Streptomyces thermotolerans, confers on Streptomyces lividans high-level resistance to the drug. However, ribosomes from S. lividans expressing carB show only moderate resistance to this macrolide in vitro, although they are highly resistant to the action of lincosamide antibiotics. The carB product monomethylates the amino group of the adenosine residue located at position 2058 in 23S ribosomal RNA. In contrast, ribosomes from S. lividans expressing ermE, in which 23S RNA is dimethylated at this same position, are much more highly resistant to macrolides and insensitive to lincosamides.

Bacterial Proteins↗
PubMed1955

Carbomycin.

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Leucomycins↗