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Journal of Bacteriology, May 1999, p. 3025-3032, Vol. 181, No. 10
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Phosphate Control of Oxytetracycline Production by Streptomyces rimosus Is at the Level of Transcription from Promoters Overlapped by Tandem Repeats Similar to Those of the DNA-Binding Sites of the OmpR Family

Kenneth J. McDowall,1 Arinthip Thamchaipenet,2 and Iain S. Hunter3,*

Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT,1 and Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G1 1QW,3 United Kingdom, and Department of Genetics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand2

Received 30 November 1998/Accepted 22 February 1999

Physiological studies have shown that Streptomyces rimosus produces the polyketide antibiotic oxytetracycline abundantly when its mycelial growth is limited by phosphate starvation. We show here that transcripts originating from the promoter for one of the biosynthetic genes, otcC (encoding anhydrotetracycline oxygenase), and from a promoter for the divergent otcX genes peak in abundance at the onset of antibiotic production induced by phosphate starvation, indicating that the synthesis of oxytetracycline is controlled, at least in part, at the level of transcription. Furthermore, analysis of the sequences of the promoters for otcC, otcX, and the polyketide synthase (otcY) genes revealed tandem repeats having significant similarity to the DNA-binding sites of ActII-Orf4 and DnrI, which are Streptomyces antibiotic regulatory proteins (SARPs) related to the OmpR family of transcription activators. Together, the above results suggest that oxytetracycline production by S. rimosus requires a SARP-like transcription factor that is either produced or activated or both under conditions of low phosphate concentrations. We also provide evidence consistent with the otrA resistance gene being cotranscribed with otcC as part of a polycistronic message, suggesting a simple mechanism of coordinate regulation which ensures that resistance to the antibiotic increases in proportion to production.

* Corresponding author. Mailing address: Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G1 1QW, United Kingdom. Phone: 44 (0) 141 548 4111. Fax: 44 (0) 141 548 4124. E-mail: i.s.hunter{at}strath.ac.uk.

Journal of Bacteriology, May 1999, p. 3025-3032, Vol. 181, No. 10
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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