Phosphate control of oxytetracycline production by Streptomyces rimosus isat the level of transcription from promoters overlapped by tandem repeats similar to those of the DNA-binding sites of the OmpR family

Physiological studies have shown that Streptomyces rimosus produces the pol yketide antibiotic oxytetracycline abundantly when its mycelial growth is l imited by phosphate starvation. We show here that transcripts originating f rom the promoter for one of the biosynthetic genes, otcC (encoding anhydrot etracycline oxygenase), and from a promoter for the divergent otcX genes pe ak 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 D NA-binding sites of ActII-Orf4 and DnrI, which are Streptomyces antibiotic regulatory proteins (SARPs) related to the OmpR family of transcription act ivators. Together, the above results suggest that oxytetracycline productio n by S. rimosus requires a SARP-like transcription factor that is either pr oduced or activated or both under conditions of low phosphate concentration s. We also provide evidence consistent with the otrA resistance gene being cotranscribed with otcC as part of a polycistronic message, suggesting a si mple mechanism of coordinate regulation which ensures that resistance to th e antibiotic increases in proportion to production.