Aziridine-Containing Natural Products: Structural Diversity, Biological Activity, Biosynthesis, and Structural Reassessment

Abstract Aziridine-containing natural products represent one of the rarest classes of nitrogen-containing secondary metabolites and comprise a structurally diverse yet remarkably understudied family. To date, only 53 aziridine-containing natural products and closely related congeners have been reported from marine organisms, plants, fungi, and predominantly actinomycetes. In addition, seven natural products originally assigned aziridine-containing structures have subsequently undergone structural reassignment, underscoring the important role of synthetic and spectroscopic studies in natural product structure elucidation. Despite their limited occurrence, these metabolites exhibit exceptional structural diversity and possess a wide range of biological activities, including antibacterial, antitumor, antifungal, antiviral, and enzyme-inhibitory properties, highlighting their considerable pharmacological potential. Recent advances in biosynthetic investigations, enzymology, and genome mining have substantially expanded our understanding of aziridine ring formation and the genetic basis underlying the biosynthesis of these metabolites. This review provides the first comprehensive overview of aziridine-containing natural products in two decades, covering their discovery, structural diversity, biological activities, biosynthetic pathways, and notable examples of structural reassignment. Current challenges, emerging trends, and future perspectives are also discussed to emphasize opportunities for the discovery, characterization, and biosynthetic exploration of new aziridine-containing natural products.