text: Innovative approach for improvement of an antibiotic-overproducing industrial strain of Streptomyces albus.
  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 beta 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.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T1 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: K88R 70S complex 70S complex rpsL ribosomal protein S12 rpoB RNA polymerase beta K88R S12 salinomycin Mg(2+) salinomycin salinomycin streptomycin gentamicin rifampin salinomycin salinomycin