Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone

Dauer consequences The dauer form in the nematode C. elegans is a non-ageing stage of the life cycle conducive to survival in adverse conditions such as food shortage. The properties of the natural dauer-inducing pheromone (‘daumone’) that regulates ageing and development in C. elegans have been studied for many years, but its precise biochemical identity remained unknown. Daumone has now been purified and fully characterized and, as predicted, it is a fatty acid derivative. Natural and chemically synthesized daumones equally induce dauer larva formation. This work could lead to novel antinematodal drugs and is relevant to research into ageing and obesity. Pheromones are cell type-specific signals used for communication between individuals of the same species. When faced with overcrowding or starvation, Caenorhabditis elegans secrete the pheromone daumone, which facilitates communication between individuals for adaptation to adverse environmental stimuli 1 , 2 , 3 , 4 . Daumone signals C. elegans to enter the dauer stage, an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life. Because daumone is a key regulator of chemosensory processes in development and ageing 5 , 6 , the chemical identification of daumone is important for elucidating features of the daumone-mediated signalling pathway. Here we report the isolation of natural daumone from C. elegans by large-scale purification, as well as the total chemical synthesis of daumone. We present the stereospecific chemical structure of purified daumone, a fatty acid derivative. We demonstrate that both natural and chemically synthesized daumones equally induce dauer larva formation in C. elegans (N2 strain) and certain dauer mutants, and also result in competition between food and daumone. These results should help to elucidate the daumone-mediated signalling pathway, which might in turn influence ageing and obesity research and the development of antinematodal drugs.