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Cyclic AMP receptor protein (Crp) is a transcription regulator controlling diverse cellular processes in many bacteria. In Streptomyces coelicolor, it is well established that Crp plays a critical role in spore germination and colony development. Here, we demonstrate that Crp is a key regulator of secondary metabolism and antibiotic production in S. coelicolor and show that it may additionally coordinate precursor flux from primary to secondary metabolism. We found that crp deletion adversely affected the synthesis of three well-characterized antibiotics in S. coelicolor: actinorhodin (Act), undecylprodigiosin (Red), and calcium-dependent antibiotic (CDA). Using chromatin immunoprecipitation-microarray (ChIP-chip) assays, we determined that eight (out of 22) secondary metabolic clusters encoded by S. coelicolor contained Crp-associated sites. We followed the effect of Crp induction using transcription profiling …