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Improvement of A21978C production in Streptomyces roseosporus by reporter-guided rpsL mutation selection.
- Source :
- Journal of Applied Microbiology; Jun2012, Vol. 112 Issue 6, p1095-1101, 7p
- Publication Year :
- 2012
-
Abstract
- Aims: Daptomycin, one of the A21978C factors produced by Streptomyces roseosporus, is an acidic cyclic lipopeptide antibiotic with potent activity against a variety of Gram-positive pathogens. To increase the titre of this extensively used and clinically important antibiotic, we applied a reported-guided rpsL mutation selection system to generate strains producing high levels of A21978C. Methods and Results: In the reporter design, dptE was chosen as the overexpressing target, and neo-encoding neomycin phosphotransferase as the reporter. Using this reporter-guided selection system, 20% of the selected, streptomycin-resistant mutants produced greater amounts of A21978C than the starting strain. The selection system increased the screening efficiency about 10-fold with a frequency of 1·7% A21978C overproducing strains among str<superscript> r</superscript> mutants. A21978C production was increased approximately 2·2-fold in the rpsL K43N mutant. Conclusions: The combination of ribosome engineering and reporter-guided mutant selection generated an A21978C overproducing strain that produced about twice as much A21978C as the parental strain. Significance and Impact of the Study: The strategies presented here, which integrated the advantages of both ribosome engineering and reporter-guided mutation selection, could be applied to other bacteria to improve their yield of secondary metabolites. [ABSTRACT FROM AUTHOR]
- Subjects :
- STREPTOMYCES
GENETIC mutation
ANTIBIOTICS
GRAM-positive bacteria
PHOSPHOTRANSFERASES
Subjects
Details
- Language :
- English
- ISSN :
- 13645072
- Volume :
- 112
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Journal of Applied Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 75126288
- Full Text :
- https://doi.org/10.1111/j.1365-2672.2012.05302.x