Bio-inspired engineering of thiopeptide antibiotics advances the expansion of molecular diversity and utility

Thiopeptide antibiotics, which are a class of sulfur-rich and highly modified peptide natural products, exhibit a wide variety of important biological properties. These antibiotics are ribosomally synthesized and arise from post-translational modifications, exemplifying a process through which nature develops the structural complexity from Ser/Thr and Cys-rich precursor peptides. Following a brief review of the knowledge gained from nature in terms of the formation of a common thiopeptide scaffold and its specialization to individual members, we highlight the significance of bio-inspired engineering, which has greatly expanded the molecular diversity and utility of thiopeptide antibiotics regarding the search for clinically useful agents, investigation into new mechanisms of action and access to typically 'inaccessible' biosynthetic processes over the past two years.