Deciphering mechanisms of production of natural compounds using inducer-producer microbial consortia

Living organisms produce a wide range of metabolites. Because of their potential antibacterial, antifungal, antiviral, or cytostatic properties, such natural molecules are of high interest to the pharmaceutical industry. In nature, these metabolites are often synthesized via secondary metabolic biosynthetic gene clusters that are silent under the typical culturing conditions. Among different techniques used to activate these silent gene clusters, co-culturing of "producer" species with specific "inducer" microbes is a particularly appealing approach due to its simplicity. Although several "inducer-producer" microbial consortia have been reported in the literature and hundreds of different secondary metabolites with attractive biopharmaceutical properties have been described as a result of co-cultivating inducer-producer consortia, less attention has been devoted to the understanding of the mechanisms and possible means of induction for production of secondary metabolites in co-cultures. This lack of understanding of fundamental biological functions and inter-species interactions significantly limits the diversity and yield of valuable compounds using biological engineering tools. In this review, we summarize and categorize the known physiological mechanisms of production of secondary metabolites in inducer-producer consortia, and then discuss approaches that could be exploited to optimize the discovery and production of secondary metabolites.