Biosynthesis of thiopeptide antibiotics and their pathway engineering

Thiopeptide antibiotics, a growing class of highly modified polythiazolyl peptides, have long been known for their remarkable bioactivities and unusual modes of actions. Uncovering of the ribosomal origin of thiopeptides now sets the stage for appreciating the initially undervalued modifications of the precursor peptides to afford the astonishing structure complexity. In this Highlight, we discuss the advances during the past four years in understanding the generality and specificity of thiopeptide biosynthesis, and on this basis, in expanding the structural diversity by pathway engineering.