DOI: 10.1128/aem.67.4.1885-1892.2001. Novel Approach for Improving the Productivity of Antibiotic-Producing Strains by Inducing Combined Resistant Mutations

Novel Approach for Improving the Productivity of Antibiotic-Producing Strains by Inducing Combined Resistant Mutations

10.1128/aem.67.4.1885-1892.2001

Crossref journal-article

American Society for Microbiology

Applied and Environmental Microbiology (235)

Abstract

ABSTRACT We developed a novel approach for improving the production of antibiotic from Streptomyces coelicolor A3(2) by inducing combined drug-resistant mutations. Mutants with enhanced (1.6- to 3-fold-higher) actinorhodin production were detected at a high frequency (5 to 10%) among isolates resistant to streptomycin (Str r ), gentamicin (Gen r ), or rifampin (Rif r ), which developed spontaneously on agar plates which contained one of the three drugs. Construction of double mutants ( str gen and str rif ) by introducing gentamicin or rifampin resistance into an str mutant resulted in further increased (1.7- to 2.5-fold-higher) actinorhodin productivity. Likewise, triple mutants ( str gen rif ) thus constructed were found to have an even greater ability for producing the antibiotic, eventually generating a mutant able to produce 48 times more actinorhodin than the wild-type strain. Analysis of str mutants revealed that a point mutation occurred within the rpsL gene, which encodes the ribosomal protein S12. rif mutants were found to have a point mutation in the rpoB gene, which encodes the β-subunit of RNA polymerase. Mutation points in gen mutants still remain unknown. These single, double, and triple mutants displayed in hierarchical order a remarkable increase in the production of ActII-ORF4, a pathway-specific regulatory protein, as determined by Western blotting analysis. This reflects the same hierarchical order observed for the increase in actinorhodin production. The superior ability of the triple mutants was demonstrated by physiological analyses under various cultural conditions. We conclude that by inducing combined drug-resistant mutations we can continuously increase the production of antibiotic in a stepwise manner. This new breeding approach could be especially effective for initially improving the production of antibiotics from wild-type strains.

Bibliography

Hu, H., & Ochi, K. (2001). Novel Approach for Improving the Productivity of Antibiotic-Producing Strains by Inducing Combined Resistant Mutations. Applied and Environmental Microbiology, 67(4), 1885â1892.

Authors 2

Haifeng Hu (first)
Kozo Ochi (additional)

References 60 Referenced 97

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Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 6:03 a.m.)
Deposited	3 years, 6 months ago (Feb. 23, 2022, 6:18 a.m.)
Indexed	14 hours, 50 minutes ago (Sept. 4, 2025, 9:54 a.m.)
Issued	24 years, 5 months ago (April 1, 2001)
Published	24 years, 5 months ago (April 1, 2001)
Published Print	24 years, 5 months ago (April 1, 2001)

Funders 0

None

BibTeX

@article{Hu_2001, title={Novel Approach for Improving the Productivity of Antibiotic-Producing Strains by Inducing Combined Resistant Mutations}, volume={67}, ISSN={1098-5336}, url={http://dx.doi.org/10.1128/aem.67.4.1885-1892.2001}, DOI={10.1128/aem.67.4.1885-1892.2001}, number={4}, journal={Applied and Environmental Microbiology}, publisher={American Society for Microbiology}, author={Hu, Haifeng and Ochi, Kozo}, year={2001}, month=apr, pages={1885–1892} }

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