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Antimicrobial Agents and Chemotherapy, March 2009, p. 1019-1026, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00388-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Novel Insertion Mutation in Streptomyces coelicolor Ribosomal S12 Protein Results in Paromomycin Resistance and Antibiotic Overproduction{triangledown}

Guojun Wang, Takashi Inaoka, Susumu Okamoto, and Kozo Ochi*

National Food Research Institute, Tsukuba, Ibaraki 305-8642, Japan

Received 22 March 2008/ Returned for modification 18 May 2008/ Accepted 11 December 2008

We identified a novel paromomycin resistance-associated mutation in rpsL, caused by the insertion of a glycine residue at position 92, in Streptomyces coelicolor ribosomal protein S12. This insertion mutation (GI92) resulted in a 20-fold increase in the paromomycin resistance level. In combination with another S12 mutation, K88E, the GI92 mutation markedly enhanced the production of the blue-colored polyketide antibiotic actinorhodin and the red-colored antibiotic undecylprodigiosin. The gene replacement experiments demonstrated that the K88E-GI92 double mutation in the rpsL gene was responsible for the marked enhancement of antibiotic production observed. Ribosomes with the K88E-GI92 double mutation were characterized by error restrictiveness (i.e., hyperaccuracy). Using a cell-free translation system, we found that mutant ribosomes harboring the K88E-GI92 double mutation but not ribosomes harboring the GI92 mutation alone displayed sixfold greater translation activity relative to that of the wild-type ribosomes at late growth phase. This resulted in the overproduction of actinorhodin, caused by the transcriptional activation of the pathway-specific regulatory gene actII-orf4, possibly due to the increased translation of transcripts encoding activators of actII-orf4. The mutant with the K88E-GI92 double mutation accumulated a high level of ribosome recycling factor at late stationary phase, underlying the high level of protein synthesis activity observed.

* Corresponding author. Mailing address: National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki, 305-8642 Japan. Phone: 81-29-838-8125. Fax: 81-29-838-7996. E-mail: kochi{at}affrc.go.jp

{triangledown} Published ahead of print on 22 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 1019-1026, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00388-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tanaka, Y., Komatsu, M., Okamoto, S., Tokuyama, S., Kaji, A., Ikeda, H., Ochi, K. (2009). Antibiotic Overproduction by rpsL and rsmG Mutants of Various Actinomycetes. Appl. Environ. Microbiol. 75: 4919-4922 [Abstract] [Full Text]  


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