Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans

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 s...

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Main Authors: Yue Zhou, Yuting Wang, Xinxing Zhang, Subhradeep Bhar, Rachel A Jones Lipinski, Jungsoo Han, Likui Feng, Rebecca A Butcher
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/33286
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author Yue Zhou
Yuting Wang
Xinxing Zhang
Subhradeep Bhar
Rachel A Jones Lipinski
Jungsoo Han
Likui Feng
Rebecca A Butcher
author_facet Yue Zhou
Yuting Wang
Xinxing Zhang
Subhradeep Bhar
Rachel A Jones Lipinski
Jungsoo Han
Likui Feng
Rebecca A Butcher
author_sort Yue Zhou
collection DOAJ
description 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.
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spelling doaj.art-acf6ca6432ea4adb932ae7285af1b13d2022-12-22T02:05:09ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.33286Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegansYue Zhou0Yuting Wang1Xinxing Zhang2Subhradeep Bhar3Rachel A Jones Lipinski4Jungsoo Han5Likui Feng6Rebecca A Butcher7https://orcid.org/0000-0002-0925-4459Department of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesDepartment of Chemistry, University of Florida, Gainesville, United StatesCaenorhabditis 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.https://elifesciences.org/articles/33286ascarosidesdauer pheromonebeta-oxidationacyl-CoA synthetaseacyl-CoA oxidaseperoxisome
spellingShingle Yue Zhou
Yuting Wang
Xinxing Zhang
Subhradeep Bhar
Rachel A Jones Lipinski
Jungsoo Han
Likui Feng
Rebecca A Butcher
Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans
eLife
ascarosides
dauer pheromone
beta-oxidation
acyl-CoA synthetase
acyl-CoA oxidase
peroxisome
title Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans
title_full Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans
title_fullStr Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans
title_full_unstemmed Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans
title_short Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans
title_sort biosynthetic tailoring of existing ascaroside pheromones alters their biological function in c elegans
topic ascarosides
dauer pheromone
beta-oxidation
acyl-CoA synthetase
acyl-CoA oxidase
peroxisome
url https://elifesciences.org/articles/33286
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