New natural products to meet the antibiotic crisis: a personal journey

The use of natural products and their derivatives has evolved as a promising approach for the treatment of various infectious diseases, particularly to combat drug-resistant microbial strains. In addition, these natural products characterized by the presence of novel structures and mechanisms of action may provide guidance toward the development of potential new chemotherapies. In the present review, antimicrobial resistance (AMR) is briefly introduced and research focused on the identification and characterization of actinomycete metabolites for antimicrobial activity is discussed. Three compounds, i.e., walkmycin B, waldiomycin, and signamycin B, with novel mechanisms of action as histidine kinase inhibitors, were isolated from the metabolites of actinomycetes. New antituberculosis antibiotics, tuberlactomicin A and caprazamycins, were discovered, and amycolamicin was identified as an antimethicillin-resistant Staphylococus aureus antibiotic. The discovery of these compounds encourages the discovery and investigation of more natural products active against antimicrobial-resistant species, thus providing scaffold for the development of effective drugs against various AMR species.