cyclodepsipeptides

Cyclodepsipeptides are macrocyclic natural products in which the ring is built from alternating amino acid and hydroxy acid residues linked by both amide and ester bonds. The ring therefore contains at least one ester linkage (a lactone) in addition to peptide bonds, distinguishing cyclodepsipeptides from ordinary cyclic peptides. Their structures often include unusual or modified amino acids and hydroxy acids, and they display a range of ring sizes from relatively small to large macrocycles.

They are produced mainly by microorganisms, including fungi such as Fusarium and Beauveria, and by certain bacteria. Biosynthesis typically proceeds via nonribosomal peptide synthetases that incorporate both amino acids and hydroxy acids and then cyclize the product to form the macrocycle.

Biological activities are diverse. Many cyclodepsipeptides act as ionophores, forming channels in membranes and disrupting ion gradients (for example valinomycin is a potassium ionophore). Others show antimicrobial, antifungal, cytotoxic, or insecticidal activities. Some are considered toxins in food safety contexts, such as enniatins produced by Fusarium species on cereals.

Representative examples include valinomycin, a well-known potassium ionophore; enniatins, cyclic hexadepsipeptides that disrupt membranes; and destruxins, insecticidal cyclodepsipeptides produced by entomopathogenic fungi. Beauveriolides and related compounds are another class of cyclodepsipeptides with varied bioactivities.

Because of their structural diversity and potent bioactivities, cyclodepsipeptides are of interest as leads in drug discovery and as tools for studying membrane transport, while their toxicity and environmental impact motivate ongoing safety assessments in agriculture and food supply.