Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

Proceedings of the National Academy of Sciences of the United States of America
Xinxing ZhangRebecca A Butcher

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 precur...Continue Reading

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Citations

Jun 15, 2015·Archives of Biochemistry and Biophysics·Michael Witting, Philippe Schmitt-Kopplin
May 18, 2016·Molecular Biology and Evolution·Gabriel V MarkovRalf J Sommer
Aug 9, 2016·Nature Chemical Biology·Qingyao ShouRebecca A Butcher
Aug 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Xinxing ZhangRebecca A Butcher
Apr 8, 2017·Natural Product Reports·Rebecca A Butcher
May 18, 2017·Nature Chemical Biology·Rebecca A Butcher
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Jul 25, 2020·Journal of the American Chemical Society·Nasser FaghihRebecca A Butcher
Feb 6, 2018·Journal of the American Chemical Society·Alexander B ArtyukhinFrank C Schroeder
Aug 22, 2021·Science Advances·Jadiel A WassonSusan E Mango

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