<jats:title>Abstract</jats:title><jats:p>Kasumigamide is an antialgal hybrid peptide–polyketide isolated from the freshwater cyanobacterium <jats:italic>Microcystis aeruginosa</jats:italic> (NIES‐87). The biosynthetic gene cluster was identified from not only the cyanobacterium but also <jats:italic>Candidatus</jats:italic> “Entotheonella”, associated with the Japanese marine sponge <jats:italic>Discodermia calyx</jats:italic>. Therefore, kasumigamide is considered to play a key role in microbial ecology, regardless of the terrestrial and marine habitats. We now report synthetic studies on this intriguing natural product that have led to a structural revision and the first total synthesis. During this study, a new analogue, deoxykasumigamide, was also isolated and structurally validated. This study confirmed the presence of the unusual pathway in the biosynthesis of a hybrid peptide–polyketide natural product.