Innovative approach for improvement of an antibiotic-overproducing industrial strain of Streptomyces albus.
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Tamehiro N, Hosaka T, Xu J, Hu H, Otake N, Ochi K
Innovative approach for improvement of an antibiotic-overproducing industrial strain of Streptomyces albus.
Appl Environ Microbiol. 2003 Nov;69(11):6412-7.
- PubMed ID
- 14602594 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Gentamicin 30S ribosomal protein S12 Protein Escherichia coli (strain K12) YesBinderDetails Gentamicin C1a 30S ribosomal protein S12 Protein Escherichia coli (strain K12) YesAdductDetails