Induction of ppGpp synthesis in Streptomyces coelicolor A3(2) grown under conditions of nutritional sufficiency elicits actII-ORF4 transcription and actinorhodin biosynthesis

Production of ppGpp in Streptomyces coelicolor A3(2) was achieved independently of amino acid limitation by placing N-terminal segments of the ppGpp synthetase gene, relA, under the control of a thiostrepton-inducible promoter (tipAp). S1 nuclease protection experiments indicated that induced ppGpp concentrations of 6-12 pmol mg(-1) dry weight in late-exponential phase cultures caused activation of transcription of actII-ORF4, the pathway-specific activator gene for actinorhodin production. This level of ppGpp had no effect on growth rate, implying a causal role for ppGpp in activating actII-ORF4 transcription. No effect was observed on the transcription of the corresponding and homologous activator gene for undecylprodigiosin production, redD, reflecting a requirement for additional regulatory factors for activation of its transcription. This work provides the most compelling evidence yet for the activation of an antibiotic biosynthetic pathway by the stringent factor ppGpp.