Actinomycetes: a still to-tap source of bioactive secondary metabolites

According to the World Health Organization, antibiotic resistance, namely the ability of bacteria to survive and replicate in the presence of an antimicrobial drug, is today one of the biggest threats to global health. Thus, the challenge of the pharmaceutical industry is to develop novel antibiotics. Secondary metabolites are low molecular weight molecules with complex chemical structures and biological activities, such as antibiotics, antitumor agents, immunosuppressive agents, inhibitors, and enzymes. Actinomycetes are the most economically and biologically precious bacteria for producing secondary metabolites of industrial interest. Actinomycetes are Gram-positive bacteria characterized by a complex morphological and physiological differentiation, featuring genomes with a high GC content, and commonly found in soil. We aim to search for new actinomycetes in unexplored niches (i.e., hydrothermal vents, activated sludge, and cultural artefacts) to discover new bioactive compounds. So far, our collection consists of hundreds of actinomycetes. 108 soil isolates were evaluated for the production of novel antibiotics against Gram-positive and negative bacteria with a multi- resistance profile. Ten potential antibiotic producers were collected and used for metabolomic analysis to evaluate the production of secondary metabolites. In addition, novel cultivation strategies and epigenetic approaches have been undertaken to enhance the discovery of new secondary metabolites holding intriguing antimicrobial activities.