Title: | A Large Family of Enzymes Responsible for the Modular Architecture of Nematode Pheromones |
Author(s): | Faghih N; Bhar S; Zhou Y; Dar AR; Mai K; Bailey LS; Basso KB; Butcher RA; |
Address: | "Department of Chemistry, University of Florida, Gainesville, Florida, United States" |
ISSN/ISBN: | 1520-5126 (Electronic) 0002-7863 (Print) 0002-7863 (Linking) |
Abstract: | "The nematode Caenorhabditis elegans produces a broad family of pheromones, known as the ascarosides, that are modified with a variety of groups derived from primary metabolism. These modifications are essential for the diverse activities of the ascarosides in development and various behaviors, including attraction, aggregation, avoidance, and foraging. The mechanism by which these different groups are added to the ascarosides is poorly understood. Here, we identify a family of over 30 enzymes, which are homologous to mammalian carboxylesterase (CES) enzymes, and show that a number of these enzymes are responsible for the selective addition of specific modifications to the ascarosides. Through stable isotope feeding experiments, we demonstrate the in vivo activity of the CES-like enzymes and provide direct evidence that the acyl-CoA synthetase ACS-7, which was previously implicated in the attachment of certain modifications to the ascarosides in C. elegans, instead activates the side chains of certain ascarosides for shortening through beta-oxidation. Our data provide a key to the combinatorial logic that gives rise to different modified ascarosides, which should greatly facilitate the exploration of the specific biological functions of these pheromones in the worm" |
Keywords: | Animals Caenorhabditis elegans/*enzymology Carboxylesterase/*metabolism Coenzyme A Ligases/*metabolism Glycolipids/biosynthesis/chemistry Molecular Structure; |
Notes: | "MedlineFaghih, Nasser Bhar, Subhradeep Zhou, Yue Dar, Abdul Rouf Mai, Kevin Bailey, Laura S Basso, Kari B Butcher, Rebecca A eng P40 OD010440/OD/NIH HHS/ R01 GM118775/GM/NIGMS NIH HHS/ S10 OD021758/OD/NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. 2020/07/25 J Am Chem Soc. 2020 Aug 12; 142(32):13645-13650. doi: 10.1021/jacs.0c04223. Epub 2020 Jul 30" |