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.