Chapter 19 - Regulation and Role of Metal Ions in Secondary Metabolite Production by Microorganisms

Abstract

Microorganisms are widely recognized for their ability to produce a wealth of natural products with structural complexity and diverse biological activities having discrete pharmaceutical and biotechnological applications. In microbes, several genes responsible for the biosynthesis of secondary metabolites are arranged in gene clusters, which are coordinately regulated by the cluster-specific transcription factors. Nevertheless, a large fraction of secondary metabolites encoded within the microbial genomes remains unexplored probably because these genes are not expressed under classical laboratory conditions. Significant research has been done in the recent years to unlock/induce these undiscovered cryptic biosynthetic gene clusters and in many cases successfully accessed to identify unknown secondary metabolites by employing biological, chemical and molecular elicitation strategies. However, cultivation-based approaches specifically, cocultivation by subjecting an inducer and a recipient microorganism culture conditions as well as external cues has long been recognized as an effective strategy to activate cryptic biosynthetic gene clusters and inducing significant changes in the microbial metabolome. Under this traditional strategy, the alteration by the mean of variation in metal ions composition is the simplest and most effective approach to provoke the expression of unexpressed or poorly expressed cryptic biosynthetic gene clusters and to realize the metabolic potential of a microbial strain under fermentation conditions. It has been appreciated for a long time that the trace metals are one of the most crucial factors which influence the production of secondary metabolites in microbes. However, the lack of precise information on the regulation of biosynthetic machinery by metal ions signals makes the research on stimulating cryptic gene clusters a challenging task. In this sense, the application of multidisciplinary approach such as genome mining, gene expression analyses with elicitation approaches with the help of bioinformatic algorithms tools can help in identification, activation and exploration of the full chemical diversity of various putative cryptic gene clusters which can provide a new avenue to the treasure trove of secondary metabolites from microorganisms. This traditional strategy can pave the way to the discovery of a plethora of secondary metabolites for pharmaceutical applications with the potential to rejuvenate stalled drug discovery pipelines. Hence this review highlights the ascribed role of metal ions in regulation of secondary metabolite production by microorganisms during fermentation processes.