title: Succinylated octopamine ascarosides and a new pathway of biogenic amine metabolism in Caenorhabditis elegans.
abstract: The ascarosides, small-molecule signals derived from combinatorial assembly of primary metabolism-derived building blocks, play a central role in Caenorhabditis elegans biology and regulate many aspects of development and behavior in this model organism as well as in other nematodes. Using HPLC-MS/MS-based targeted metabolomics, we identified novel ascarosides incorporating a side chain derived from succinylation of the neurotransmitter octopamine. These compounds, named osas#2, osas#9, and osas#10, are produced predominantly by L1 larvae, where they serve as part of a dispersal signal, whereas these ascarosides are largely absent from the metabolomes of other life stages. Investigating the biogenesis of these octopamine-derived ascarosides, we found that succinylation represents a previously unrecognized pathway of biogenic amine metabolism. At physiological concentrations, the neurotransmitters serotonin, dopamine, and octopamine are converted to a large extent into the corresponding succinates, in addition to the previously described acetates. Chemically, bimodal deactivation of biogenic amines via acetylation and succinylation parallels posttranslational modification of proteins via acetylation and succinylation of L-lysine. Our results reveal a small-molecule connection between neurotransmitter signaling and interorganismal regulation of behavior and suggest that ascaroside biosynthesis is based in part on co-option of degradative biochemical pathways.
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Artyukhin
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Yim
authors.forename: Jagan
authors.initials: J
authors.lastname: Srinivasan
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Izrayelit
authors.forename: Neelanjan
authors.initials: N
authors.lastname: Bose
authors.forename: Stephan H
authors.initials: SH
authors.lastname: von Reuss
authors.forename: Yeara
authors.initials: Y
authors.lastname: Jo
authors.forename: James M
authors.initials: JM
authors.lastname: Jordan
authors.forename: L Ryan
authors.initials: LR
authors.lastname: Baugh
authors.forename: Micheong
authors.initials: M
authors.lastname: Cheong
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.forename: Leon
authors.initials: L
authors.lastname: Avery
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schroeder
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000737:chemistry; D000818:Animals; D001522:Behavior, Animal; D001679:Biogenic Amines / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry; D013058:Mass Spectrometry; D018377:Neurotransmitter Agents / Q000378:metabolism; D009655:Octopamine / Q000737:chemistry*; D010675:Pheromones / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D013386:Succinates / Q000737:chemistry
chemical_list: D000316:Adrenergic alpha-Agonists; D001679:Biogenic Amines; D006027:Glycosides; D018377:Neurotransmitter Agents; D010675:Pheromones; D013386:Succinates; D009655:Octopamine; D012701:Serotonin; D004298:Dopamine
keywords: Biosynthesis; Dauer; Dopamine; Neurotransmitters; Pheromone; Serotonin; Small-molecule signaling