An acyl-CoA thioesterase is essential for the biosynthesis of a key dauer pheromone in C. elegans.

Autor:	Bhar S; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Yoon CS; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Mai K; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Han J; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Prajapati DV; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Wang Y; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Steffen CL; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Bailey LS; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Basso KB; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA., Butcher RA; Department of Chemistry, University of Florida, Gainesville, FL 32611, USA. Electronic address: butcher@chem.ufl.edu.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2024 May 16; Vol. 31 (5), pp. 1011-1022.e6. Date of Electronic Publication: 2024 Jan 05.
DOI:	10.1016/j.chembiol.2023.12.006
Abstrakt:	Methyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans, including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the β-keto acyl-CoA side chain of an ascaroside intermediate during β-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The β-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, 1). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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