Recent advance in macrolactams: Structure, bioactivity, and biosynthesis

Macrolactams have garnered significant attention in recent years due to their diverse structures and remarkable biological activities. Despite the increasing number of new members being reported, a systematic discussion of recent advancements in this family is still lacking, particularly in areas such as structure-activity relationship and newly identified biosynthetic pathways that deviate from the traditional collinear rule. To address this gap, we compiled 105 macrolactams reported between 2004 and 2023, produced by microbial strains isolated from diverse environments, including marine sediments, soil, plants, and animals. This review not only highlights the sources, structures, and biological activities of these macrolactams but also delves into 17 known biosynthetic pathways. We provide an in-depth analysis of the associated biosynthetic gene clusters, the mechanisms of key enzymes, and their roles in the biosynthesis process. By offering these insights, this review serves as a valuable reference for the discovery of novel macrolactams and their sustainable production using synthetic biology approaches in the future.