Zhou, Y. et al. (2019) International Worm Meeting "Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans."

Lipinski, R.A.J., Zhang, X., Feng, L., Han, J., Zhou, Y., Wang, Y., Bhar, S., Butcher, R.A.

[International Worm Meeting, 2019]

Caenorhabditis elegans produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we identify a mechanism that enables C. elegans to dynamically tailor the fatty-acid side chains of the indole-modified ascarosides it has produced. In response to starvation, C. elegans uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain indole-ascarosides for ?-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. This pathway thus enables the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for the biosynthesis of the indole-ascarosides in which side chain ?-oxidation is critical for controlling the type of indole-ascarosides produced.