Insights into applications and strategies for discovery of microbial bioactive metabolites

Secondary metabolites of microbial origin are structurally diverse and functionally versatile compounds that offer selective advantages to the producing organism. Production of these compounds is low under natural conditions and requires elicitation for large-scale production. Omic sciences provide a major breakthrough in the discovery of novel compounds and indicate efficiency of microorganisms to produce a diverse array of chemical entities more than those known today. Synthetic biology in particular, has remarkably changed the outlook to explore natural products by unravelling hidden potential of the microorganisms. In silico studies pave a path to investigate new secondary metabolic compounds by the fusion of genetics, chemistry, and computer science, which expand their diversity and lead to generation of new analogs. Genes involved in secondary metabolite biosynthesis, regulation and transport in microorganisms are organized into clusters known as Biosynthetic gene clusters (BGCs). Application of sophisticated tools helps to get more information on newer BGCs leading to novel bioactive compound discovery. Experimental verification and structural elucidation are still the bottleneck in the discovery of a new product, but in silico tools help to speed up the process of product prediction and its identification. They also help in optimizing strains for stable and optimal production during scale up process for an economic output. In the present study, we have described microbial secondary metabolites with special mention of polyketides (PKS) and non-ribosomal polypeptides (NRPS) along with some of the strategies employed to induce their production, providing the main emphasis on in silico methods and tools used in their study and analysis to date.