A Combinatorial Approach of High-Throughput Genomics and Mass Proteomics for Understanding the Regulation and Expression of Secondary Metabolite Production in Actinobacteria

Secondary metabolites produced by Actinobacteria are an important source of antibiotics, drugs, and antimicrobial peptides. However, the large genome size of actinobacteria with high gene coding density makes it difficult to understand the complex regulation of biosynthesis of such critically and economically important products. In the last few decades, apart from genomics sequences, high-throughput proteomics has proven beneficial to understand the key players regulating the expression pattern of secondary metabolite and antibiotic production in different experimental set-ups. In the past, we have been analyzing the genomics data and mass spectrometry-based proteomics to predict the regulation dynamics and crucial regulatory hubs in Actinobacteria. The multidirectional regulation and expression of the biosynthetic gene cluster responsible for the production of important metabolite take their cue from the other primary metabolism pathways with which they show intricate interactions in the interactome. The regulation occurs by not only the action and expression of the biosynthetic gene cluster but also the role of transcription factors and primary metabolic pathways. Using the key players of these interactomes, we can regulate the synthesis/production of these valuable peptides/metabolites. Simultaneously, the multi-omics approach has now opened new gateways in investigation, screening, and identification of naturally occurring antimicrobial peptides from actinobacteria which are beneficial for humans and also provide economic and industrial benefits to humankind.