Production of Antibacterial Compounds from Actinomycetes

Actinomycetes are soil-dwelling Gram-positive bacteria, industrially relevant as producers of a wide range of bioactive secondary metabolites, including many antibiotics of clinical and commercial importance.The understanding of actinomycete biology has been based on extensive studies on the model organism Streptomyces coelicolor over many years and on the availability of its complete genome sequence. This bacterium has an unusual complex developmental cycle that includes programmed cell death phenomena that make this bacterium a multicellular prokaryotic model.Morphological differentiation in S. coelicolor is strictly related to physiological differentiation: indeed the onset of morphological differentiation generally coincides with the production of secondary metabolites. During cell death, degradative proteins are synthesized and involved in an extensive degradation of some cellular constituents (proteins and lipids) used for a second growth phase, that is accompanied by antibiotic production.If on one hand, many factors with pleiotropic activity have been identified as key players to control both morphological and physiological differentiation in S. coelicolor, on the other hand, for most actinomycetes, mechanisms and factors governing morphological and physiological processes have not been deeply investigated.This chapter reviews the regulatory mechanisms known to control antibiotic production in actinomycetes and both genetic and physiological methods adopted to improve antibiotic yields.