Polyketidepeptides

Polyketidepeptides are natural products that combine elements derived from polyketide biosynthesis with peptide-like structures. They are produced by a range of organisms, notably fungi and bacteria, and arise from hybrid biosynthetic pathways that recruit both polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). The resulting molecules often feature complex, macrocyclic or linear architectures and exhibit diverse biological activities.

Structural features commonly include depsipeptide linkages, where hydroxy acids supplied by PKS modules are incorporated into peptide backbones via ester bonds in addition to amide bonds. The products may be cyclic or open-chain, and the size and composition vary with the module organization of the PKS-NRPS assembly lines. This modular biosynthesis allows incorporation of unusual amino acids and hydroxy acid units, generating considerable chemical diversity.

Well-known examples include enniatins and beauvericin, cyclic hexadepsipeptides produced by Fusarium species. These compounds are characterized by ionophoric properties and cytotoxic effects, and they serve as tools for studying PKS-NRPS biology as well as potential leads in pharmacology. Other polyketidepeptides include a range of cyclic/depsipeptide hybrids with antimicrobial, antifungal, or anticancer activities reported in fungal and bacterial producers.

Research on polyketidepeptides focuses on understanding their gene clusters, improving heterologous production, and exploring structure–activity relationships. Advances in genome mining and synthetic biology aim to unlock new hybrids with therapeutic potential, while addressing challenges such as complex structures, supply, and safety considerations.