DOI: 10.1128/aem.02800-07. Dramatic Activation of Antibiotic Production in <i>Streptomyces coelicolor</i> by Cumulative Drug Resistance Mutations

Dramatic Activation of Antibiotic Production in Streptomyces coelicolor by Cumulative Drug Resistance Mutations

10.1128/aem.02800-07

Crossref journal-article

American Society for Microbiology

Applied and Environmental Microbiology (235)

Abstract

ABSTRACT We recently described a new method to activate antibiotic production in bacteria by introducing a mutation conferring resistance to a drug such as streptomycin, rifampin, paromomycin, or gentamicin. This method, however, enhanced antibiotic production by only up to an order of magnitude. Working with Streptomyces coelicolor A3(2), we established a method for the dramatic activation of antibiotic production by the sequential introduction of multiple drug resistance mutations. Septuple and octuple mutants, C7 and C8, thus obtained by screening for resistance to seven or eight drugs, produced huge amounts (1.63 g/liter) of the polyketide antibiotic actinorhodin, 180-fold higher than the level produced by the wild type. This dramatic overproduction was due to the acquisition of mutant ribosomes, with aberrant protein and ppGpp synthesis activity, as demonstrated by in vitro protein synthesis assays and by the abolition of antibiotic overproduction with relA disruption. This new approach, called “ribosome engineering,” requires less time, cost, and labor than other methods and may be widely utilized for bacterial strain improvement.

Bibliography

Wang, G., Hosaka, T., & Ochi, K. (2008). Dramatic Activation of Antibiotic Production in Streptomyces coelicolor by Cumulative Drug Resistance Mutations. Applied and Environmental Microbiology, 74(9), 2834â2840.

Authors 3

Guojun Wang (first)
Takeshi Hosaka (additional)
Kozo Ochi (additional)

References 37 Referenced 122

10.1016/S1369-5274(99)00005-3
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Wilson, D. N. 2004. Antibiotics and the inhibition of ribosome function, p. 449-527. In D. N. Wilson and K. H. Niehaus (ed.), Protein synthesis and ribosome structure: translating the genome. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. / Protein synthesis and ribosome structure: translating the genome. (2004)
10.1016/S0076-6879(06)15012-0

Dates

Type	When
Created	17 years, 6 months ago (Feb. 29, 2008, 9:37 p.m.)
Deposited	3 years, 6 months ago (Feb. 23, 2022, 11:57 a.m.)
Indexed	1 month ago (Aug. 3, 2025, 12:03 a.m.)
Issued	17 years, 4 months ago (May 1, 2008)
Published	17 years, 4 months ago (May 1, 2008)
Published Print	17 years, 4 months ago (May 1, 2008)

Funders 0

None

BibTeX

@article{Wang_2008, title={Dramatic Activation of Antibiotic Production in Streptomyces coelicolor by Cumulative Drug Resistance Mutations}, volume={74}, ISSN={1098-5336}, url={http://dx.doi.org/10.1128/aem.02800-07}, DOI={10.1128/aem.02800-07}, number={9}, journal={Applied and Environmental Microbiology}, publisher={American Society for Microbiology}, author={Wang, Guojun and Hosaka, Takeshi and Ochi, Kozo}, year={2008}, month=may, pages={2834–2840} }

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