Carbon catabolite regulation of secondary metabolite formation,an old but not well-established regulatory system

Secondary microbial metabolites have various functions for the producer microorganisms, which allow them to interact and survive in adverse environments. In addition to these functions, other biological activities may have clinical relevance, as diverse as antimicrobial, anticancer and hypocholesterolaemic effects. These metabolites are usually formed during the idiophase of growth and have a wide diversity in their chemical structures. Their synthesis is under the impact of the type and concentration of the culture media nutrients. Some of the molecular mechanisms that affect the synthesis of secondary metabolites in bacteria (Gram-positive and negative) and fungi are partially known. Moreover, all microorganisms have their peculiarities in the control mechanisms of carbon sources, even those belonging to the same genus. This regulatory knowledge is necessary to establish culture conditions and manipulation methods for genetic improvement and product fermentation. As the carbon source is one of the essential nutritional factors for antibiotic production, its study has been imperative both at the industrial and research levels. This review aims to draw the utmost recent advances performed to clarify the molecular mechanisms of the negative effect exerted by the carbon source on the secondary metabolite formation, emphasizing those found in Streptomyces, one of the genera most profitable antibiotic producers.