Actinomycetes: Treasure trove for discovering novel antibiotic candidates

Actinomycetes are an important source of secondary metabolites such as antibiotics and other active natural products. Many well-known antibiotics, such as streptomycin, oxytetracycline, and tetracycline, are produced by actinomycetes. Different types of antibiotics have distinct mechanisms of action against microorganisms: inhibit protein synthesis, inhibit nucleic acid synthesis, or inhibit cell wall synthesis. For decades, actinomycetes have played a crucial role in clinical treatment for major diseases such as pathogenic bacterial infections, serving as one of the most significant sources of new discoveries. However, due to extensive use of antibiotics, the types and numbers of drug-resistant bacteria, represented by multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, have increased dramatically in clinical settings, posing a significant threat to human survival. Therefore, there is an urgent need to search for structurally novel antibacterial natural products and develop new antibiotics. In this review, a total of 170 antibacterial secondary metabolites from actinomycetes, published in the 54 literatures (2020 to September 2024) and some synthetic analogs, are discussed with emphasis on their structures and biological activities.