title: Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans.
abstract: Caenorhabditis elegans uses ascaroside pheromones to induce development of the stress-resistant dauer larval stage and to coordinate various behaviors. Peroxisomal β-oxidation cycles are required for the biosynthesis of the fatty acid-derived side chains of the ascarosides. Here we show that three acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, form different protein homo- and heterodimers with distinct substrate preferences. Mutations in the acyl-CoA oxidase genes acox-1, -2, and -3 led to specific defects in ascaroside production. When the acyl-CoA oxidases were expressed alone or in pairs and purified, the resulting acyl-CoA oxidase homo- and heterodimers displayed different side-chain length preferences in an in vitro activity assay. Specifically, an ACOX-1 homodimer controls the production of ascarosides with side chains with nine or fewer carbons, an ACOX-1/ACOX-3 heterodimer controls the production of those with side chains with seven or fewer carbons, and an ACOX-2 homodimer controls the production of those with ω-side chains with less than five carbons. Our results support a biosynthetic model in which β-oxidation enzymes act directly on the CoA-thioesters of ascaroside biosynthetic precursors. Furthermore, we identify environmental conditions, including high temperature and low food availability, that induce the expression of acox-2 and/or acox-3 and lead to corresponding changes in ascaroside production. Thus, our work uncovers an important mechanism by which C. elegans increases the production of the most potent dauer pheromones, those with the shortest side chains, under specific environmental conditions.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611.
authors.forename: Likui
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611.
authors.forename: Satya
authors.initials: S
authors.lastname: Chinta
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611.
authors.forename: Prashant
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611.
authors.forename: Joshawna K
authors.initials: JK
authors.lastname: Nunnery
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611 butcher@chem.ufl.edu.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Butcher
mesh_terms: D042962:Acyl-CoA Oxidase / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D002384:Catalysis; D002853:Chromatography, Liquid; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D010675:Pheromones / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D055503:Protein Multimerization; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry; D013696:Temperature
chemical_list: D010675:Pheromones; D042962:Acyl-CoA Oxidase; D010100:Oxygen
keywords: acyl-CoA oxidase; ascaroside; beta-oxidation; dauer; pheromone