RRC ID 56250
Author Zhou Y, Wang Y, Zhang X, Bhar S, Jones Lipinski RA, Han J, Feng L, Butcher RA.
Title Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans.
Journal Elife
Abstract 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-3-carbonyl (IC)-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 IC-ascarosides for β-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. Thus, the pathway allows 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 biosynthesis of the IC-ascarosides in which side-chain β-oxidation is critical for controlling the type of IC-ascarosides produced.
Volume 7
Published 2018-6-4
DOI 10.7554/eLife.33286
PII 33286
PMID 29863473
PMC PMC5986272
MeSH Acyl-CoA Oxidase / metabolism Animals Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Coenzyme A Ligases / metabolism Glycolipids / biosynthesis* Glycolipids / chemistry Larva / growth & development Larva / metabolism Models, Chemical Molecular Structure Oxidation-Reduction Pheromones / biosynthesis* Pheromones / chemistry
IF 7.551
Times Cited 7
C.elegans tm6415 tm4033