<jats:title>Abstract</jats:title><jats:p>The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium <jats:italic>Photorhabdus luminescens</jats:italic>. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of <jats:sc>D</jats:sc>‐/ <jats:sc>L</jats:sc>‐peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against <jats:italic>Trypanosoma brucei rhodesiense</jats:italic>, a recalcitrant parasite that causes the deadly disease African sleeping sickness.