Cyanobacterial peptides and polyketides: biosynthetic basis, structural diversity and therapeutic relevance

Cyanobacteria are an evolutionarily ancient group of oxygenic photosynthetic prokaryotes recognized as prolific producers of structurally diverse secondary metabolites. Among these metabolites, peptides and polyketides constitute two major and classes of chemicals known for a broad-spectrum biological activities, viz. , antimicrobial, antiviral, anticancer, anti-inflammatory, enzyme inhibitory, and immunomodulatory effects. The chemical diversity of these compounds is primarily derived from non-ribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and hybrid NRPS–PKS biosynthetic pathways, which enable the incorporation of non-proteinogenic amino acids, extensive tailoring reactions, and macrocyclization. In addition, ribosomally synthesized and post-translationally modified peptides (RiPPs) further expand the structural and functional repertoire of cyanobacterial natural products. This review provides a critical overview of cyanobacterial peptides and polyketides, focusing on their biosynthetic basis, structural diversity, and biological activities relevant to phytomedicine. Major peptide and polyketide scaffolds are discussed in relation to their molecular mechanisms of action and structure–activity relationships, with particular emphasis on applications in inflammation, cancer, infectious diseases, and immune modulation. Key challenges limiting translational application, including toxicity, low natural abundance, and cryptic biosynthetic gene clusters (BGCs), are also highlighted alongside emerging biotechnological strategies.