Methods and challenges for efficient antibiotic discovery from <i>Streptomyces</i> sp.

Natural products (NPs) hold significant value across medicine, agriculture, the food industry, and biotechnology, playing a particularly crucial role in antibiotic development. Streptomyces is one of the most important antibiotic-producing bacteria, known for synthesizing a diverse range of antimicrobial compounds, including β-lactams, macrolides, glycopeptides, and tetracyclines. However, genomic analyses indicate that most Streptomyces secondary metabolite biosynthetic gene clusters (BGCs) remain silent, limiting the discovery and utilization of their potential metabolic products. In recent years, genome mining supported by bioinformatics tools and activation strategies for silent BGCs have significantly expanded the scope of novel antibiotic discovery. This review summarizes genome mining approaches for Streptomyces , strategies for activating silent BGCs, and their applications in novel antibiotic development while discussing current challenges in the field.