An acyl-CoA thioesterase is essential for the biosynthesis of a key dauer pheromone in C. elegans.

Methyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans , including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the β-keto acyl-CoA side chain of an ascaroside intermediate during β-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The β-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, 1). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm. [Display omitted] • The acyl-CoA thioesterase ACOT-15 biosynthesizes key ascaroside pheromones in worms • ACOT-15 terminates β-oxidation, producing a dauer-inducing methyl ketone ascaroside • ACOT-15 also generates a non-dauer-inducing piperidyl ascaroside • Bacterial food affects the production of the piperidyl ascaroside by the worm Bhar et al. identify an acyl-CoA thioesterase, ACOT-15, that terminates the β-oxidation pathway in pheromone biosynthesis in C. elegans and produces a key methyl ketone ascaroside that induces dauer, as well as a non-dauer-inducing piperidyl ascaroside. Bacterial food impacts the amount of the piperidyl ascaroside made by the worm. [ABSTRACT FROM AUTHOR]