Rare functional groups and unique scaffolds in Streptomyces natural products

Abstract

Covering: up to December 2025

The incorporation of distinctive structures such as uncommon functional groups, distinct molecular scaffolds, unusual modifications and other characteristic structural features can significantly enhance metabolic stability, bioactivity, and pharmacokinetic properties of drug molecules, offering ways to optimize the design and synthesis of novel bioactive molecules in synthetic biology. Streptomyces, a highly diverse and widespread bacterial genus, produces an extraordinary array of secondary metabolites, exhibiting remarkable structural variety. This structural ingenuity lies at the heart of functional innovation, establishing Streptomyces as a prolific source for drug discovery. The vast and diverse structural repertoire of these natural products offers valuable inspiration for novel structural designs in medicinal chemistry. Moreover, the vast array of natural enzymes provides a versatile toolkit for the site-specific modifications of complex scaffolds, facilitating the development of novel drug molecules that bypass the structural limitations of traditional chemical synthesis. This review highlights Streptomyces natural products with rare functional groups, unique scaffolds, and atypical modifications, examining the enzymatic mechanisms to link biosynthetic diversity with synthetic biology applications and efficient cell factory design.