Streptomycin and Related Antibiotics

Wallace, Brian; Tai, Phang C.; Davis, Bernard D.

doi:10.1007/978-3-642-46403-4_16

Cited by 18 publications

(4 citation statements)

References 203 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thiostrepton achieves the latter by inhibiting IF-1-catalyzed recycling of IF-2 (Sarkar et al, 1974): sufficient antibiotic statically traps all the added IF-2 and equivalent amounts of fMet-tRNA in immature, puromycinunreactive 70S complexes. The plateau observed with streptomycin is attributed to enhanced streptomycin-plus IF-catalyzed decomposition of 70 S-fMet-tRNA-mRNA in the cyclic steady state (Wallace et al, 1979). Neither an intrinsic nor an artifactual two-population model seems appropriate for the thermorubin results: the simple thermorubin binding isotherm (Lin & Wishnia, 1982) and the fact that binding of AcPhe-tRNA is inhibited 100% when the same ribosome and IF preparations are used (section D below) are both inconsistent either with a preexisting distribution (60% sensitive to Tr alone, 40% only to Tr plus excess uncharged tRNA) or with a fractionation by Tr into a totally inert subpopulation (by sequestration of a limiting reagent) and a subpopulation that binds fMet-tRNA very well but is completely inhibited by added tRNA.…”

Section: Resultsmentioning

confidence: 95%

The protein synthesis inhibitor thermorubin. 2. Mechanism of inhibition of initiation on Escherichia coli ribosomes

Lin¹,

Wishnia²

1982

Biochemistry

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 95%

The protein synthesis inhibitor thermorubin. 2. Mechanism of inhibition of initiation on Escherichia coli ribosomes

Lin¹,

Wishnia²

1982

Biochemistry

View full text Add to dashboard Cite

“…Although we did not attempt to identify the mutation in the present study, gentamicin resistance is known to result from a mutation in the rplF gene, which codes for the ribosomal L6 protein (10). The action of streptomycin on bacterial ribosomes has been studied in great detail (1,28), and among the numerous effects attributed to this drug, misreading of mRNA codons is the best known. Gentamicin belongs to the kanamycin class of aminoglycosides but is structurally different from streptomycin.…”

Section: Discussionmentioning

confidence: 99%

Innovative Approach for Improvement of an Antibiotic-Overproducing Industrial Strain of Streptomyces albus

Tamehiro

Hosaka

et al. 2003

Appl Environ Microbiol

View full text Add to dashboard Cite

Working with a Streptomyces albus strain that had previously been bred to produce industrial amounts (10 mg/ml) of salinomycin, we demonstrated the efficacy of introducing drug resistance-producing mutations for further strain improvement. Mutants with enhanced salinomycin production were detected at a high incidence (7 to 12%) among spontaneous isolates resistant to streptomycin (Str r ), gentamicin, or rifampin (Rif r ). Finally, we successfully demonstrated improvement of the salinomycin productivity of the industrial strain by 2.3-fold by introducing a triple mutation. The Str r mutant was shown to have a point mutation within the rpsL gene (encoding ribosomal protein S12). Likewise, the Rif r mutant possessed a mutation in the rpoB gene (encoding the RNA polymerase ␤ subunit). Increased productivity of salinomycin in the Str r mutant (containing the K88R mutation in the S12 protein) may be a result of an aberrant protein synthesis mechanism. This aberration may manifest itself as enhanced translation activity in stationary-phase cells, as we have observed with the poly(U)-directed cell-free translation system. The K88R mutant ribosome was characterized by increased 70S complex stability in low Mg 2؉ concentrations. We conclude that this aberrant protein synthesis ability in the Str r mutant, which is a result of increased stability of the 70S complex, is responsible for the remarkable salinomycin production enhancement obtained.Improvement of the productivity of commercially viable microbiotic strains is an important field in microbiology, especially since wild-type strains isolated from nature usually produce only a low level (1ϳ100 g/ml) of antibiotics. A great deal of effort and resources is therefore committed to improving antibiotic-producing strains to meet commercial requirements. Current methods of improving the productivity of industrial microorganisms range from the classical random approach to using highly rational methods, for example metabolic engineering. Although classical methods are still effective even without using genomic information or genetic tools to obtain highly productive strains, these methods are always time-and resource-intensive (27,31).Members of the genus Streptomyces produce a wide variety of secondary metabolites that include about half of the known microbial antibiotics. We reported previously that a certain str mutation that confers streptomycin resistance is able to give rise to secondary metabolite production in Streptomyces lividans and Streptomyces coelicolor A3(2) (3,20,24). Later, we demonstrated that the introduction of a specific str mutation, as well as a gentamicin resistance-producing mutation (gen), into other bacterial genera gave rise to a marked antibiotic productivity increase, thus further elucidating the antibiotic production mechanism in S. coelicolor A3(2) (6). Furthermore, by inducing a mutation that confers resistance to rifampin, we were able to restore the impaired production of antibiotics in the relA and relC mutants of S. coelicolor A3(2) (8,11,...

show abstract

“…The effects of streptomycin on bacterial ribosomes have been studied in great detail (3,4,31). Among the numerous actions attributed to this drug, its ability to cause mRNA codons to be misread is the best characterized.…”

Section: Discussionmentioning

confidence: 99%

Improvement of α-Amylase Production by Modulation of Ribosomal Component Protein S12 in Bacillus subtilis 168

Kurosawa

Hosaka

Tamehiro

et al. 2006

Appl Environ Microbiol

View full text Add to dashboard Cite

The capacity of ribosomal modification to improve antibiotic production by Streptomyces spp. has already been demonstrated. Here we show that introduction of mutations that produce streptomycin resistance (str) also enhances ␣-amylase (and protease) production by a strain of Bacillus subtilis as estimated by measuring the enzyme activity. The str mutations are point mutations within rpsL, the gene encoding the ribosomal protein S12. In vivo as well as in vitro poly(U)-directed cell-free translation systems showed that among the various rpsL mutations K56R (which corresponds to position 42 in E. coli) was particularly effective at enhancing ␣-amylase production. Cells harboring the K56R mutant ribosome exhibited enhanced translational activity during the stationary phase of cell growth. In addition, the K56R mutant ribosome exhibited increased 70S complex stability in the presence of low Mg 2؉ concentrations. We therefore conclude that the observed increase in protein synthesis activity by the K56R mutant ribosome reflects increased stability of the 70S complex and is responsible for the increase in ␣-amylase production seen in the affected strain.

show abstract

Streptomycin and Related Antibiotics

Cited by 18 publications

References 203 publications

The protein synthesis inhibitor thermorubin. 2. Mechanism of inhibition of initiation on Escherichia coli ribosomes

The protein synthesis inhibitor thermorubin. 2. Mechanism of inhibition of initiation on Escherichia coli ribosomes

Innovative Approach for Improvement of an Antibiotic-Overproducing Industrial Strain of Streptomyces albus

Improvement of α-Amylase Production by Modulation of Ribosomal Component Protein S12 in Bacillus subtilis 168

Contact Info

Product

Resources

About