The bisintercalator family of nonribosomal peptides: structural diversity and biosynthetic mechanism

Abstract

Covering: up to February 2025

Among the numerous bioactive microbial natural products, a subset of nonribosomal peptides derived from actinobacteria is characterized by their C₂-symmetric macrocyclic scaffolds and referred to as bisintercalators due to their ability to bisintercalate into DNA molecules. This family of compounds exhibits excellent antimicrobial, antitumor and antiviral properties, making them promising candidates for drug development. New members of the bisintercalator family continue to be discovered, and significant advancement has been made in understanding their biosynthesis over the past two decades. These efforts have established the general biosynthetic pathways of bisintercalators, although some chemically intriguing enzymatic transformations remain to be fully elucidated. This review summarizes the sources and chemical structures of known bisintercalators, briefly discussing their bioactivities, and then highlights the biochemical reactions involved in assembling their sophisticated macrocyclic scaffolds.