Insights for napyradiomycin family: structures, bioactivities and biosynthetic pathways

Napyradiomycins (NPDs), a family of structurally diverse terpenoids isolated from Streptomyces, have attracted significant scientific interest due to their unique halogenation patterns and potent bioactivities. Since identifying the first member from Streptomyces in 1986, over 50 NPDs have been characterized, demonstrating remarkable efficacy against drug-resistant bacteria and cancer cells, making them promising candidates for novel drug development. In this review, we provided an in-depth exploration of the complex chemical structure of NPDs, their diverse bioactivities, and the biosynthetic pathways involved in their formation. In particular, we collectively concluded the structure-activity relationship data to highlight the importance of the molecular features of napyradiomycins determining their therapeutic potential. Recent discoveries have shed light on the unique role of halogenases, which contribute to the structural diversity and enhance the biological potency of napyradiomycins, thus refining the known biosynthetic pathways. The data presented here aims to stimulate further research and facilitate the advancement of NPDs toward becoming first-line therapies for infectious diseases and cancer.