The regulation of the secondary metabolism of Streptomyces: new links and experimental advances

Streptomycetes and other actinobacteria are renowned as a rich source of natural products of clinical, agricultural and biotechnological value. They are being mined with renewed vigour, supported by genome sequencing efforts, which have revealed a coding capacity for secondary metabolites in vast excess of expectations that were based on the detection of antibiotic activities under standard laboratory conditions. Here we review what is known about the control of production of so-called secondary metabolites in streptomycetes, with an emphasis on examples where details of the underlying regulatory mechanisms are known. Intriguing links between nutritional regulators, primary and secondary metabolism and morphological development are discussed, and new data are included on the carbon control of development and antibiotic production, and on aspects of the regulation of the biosynthesis of microbial hormones. Given the tide of antibiotic resistance emerging in pathogens, this review is peppered with approaches that may expand the screening of streptomycetes for new antibiotics by awakening expression of cryptic antibiotic biosynthetic genes. New technologies are also described that have potential to greatly further our understanding of gene regulation in what is an area fertile for discovery and exploitation.