depsipeptide

A depsipeptide is a type of natural product in which one or more amide bonds of a peptide are replaced by ester bonds. In practice this means that at least one linkage in the chain is formed between the carboxyl group of an amino acid and the hydroxyl group of a hydroxy acid, yielding an ester linkage in addition to amide bonds. Depsipeptides may be linear or cyclic; cyclic variants are often referred to as cyclodepsipeptides.

Biosynthesis and occurrence: They are commonly produced by bacteria and fungi via nonribosomal peptide synthetases that incorporate hydroxy acids into the growing chain, creating ester bridges during macrocyclization. They are frequently macrocyclic and often display ionophoric, antibiotic, or cytotoxic activities.

Examples: Valinomycin is a well-known cyclic dodecadepsipeptide that acts as a potassium ion carrier; Beauvericin is a cyclic hexadepsipeptide with three hydroxy acids; Enniatins are cyclic hexadepsipeptides produced by Fusarium species.

Research and applications: They are valuable for studying structure-activity relationships; some have been explored for therapeutic potential, though their ester linkages can confer instability. Isolation and total synthesis are active areas, and chemical synthesis often requires careful protection of ester functionalities.