Cyanobacteria Join the Kahalalide Conversation: Genome and Metabolite Evidence for Structurally Related Peptides

Natural Products Chemistry, Genomics, and Bioinformatics

This preprint focuses on the discovery and characterization of kahalalide Z5 (KZ5), a cyclic depsipeptide with structural similarities to the known anticancer compound kahalalide F. The research uses established techniques like NMR, MS, and chemical degradation, combined with AI-driven tools (SMART NMR and DeepSAT) to elucidate KZ5's structure and biosynthetic pathway. The identification of a biosynthetic gene cluster in a cyanobacterium, combined with comparative genomic analysis with known kahalalide producers, contributes to expanding our understanding of these compounds. The study operates within the existing paradigm of natural products chemistry, genomics, and bioinformatics by applying standard methodologies and interpretations. It represents an extension of current knowledge rather than a challenge to existing theoretical frameworks or experimental approaches. The use of AI tools enhances the research process but does not fundamentally alter the paradigm. Therefore, it fits within the "Normal Science" classification as defined by Kuhn.