Siva Bandi, Marie-Désirée Schlemper-Scheidt, Rocío Rivera Sánchez, Sylvain Sutour, Gaétan Glauser, Yojiro Ishida and Stephan H. von Reuß*,
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引用次数: 0
Abstract
N-acyl ethanolamines represent conserved lipophilic signaling molecules that function as endogenous ligands at G-protein-coupled receptors, ion channels, and nuclear receptors. Using a combination of comparative ultrahigh-performance liquid chromatography electrospray ionization high-resolution tandem mass spectrometry (UHPLC-ESI-HR-MSE) analysis and microreactions, a diversity of glycosylated N-acyl phosphoethanolamines were characterized in Caenorhabditis nematodes. Representative examples were enriched by RP-C18 chromatography and identified by NMR spectroscopy. Comparative metabolomics and isotope incorporation experiments revealed that the biosynthesis of the homologous N-acyl building blocks (approximately 50 compounds) depends on the bacterial food source, chain elongation and desaturation of food-derived fatty acids, or their de novo biosynthesis by the nematode, whereas the biosynthesis of medium-chain N-acyl units depends on the peroxisomal β-oxidation cycle via the 3-ketoacyl-S-CoA thiolase daf-22. Glycosylation of these lipophilic N-acyl ethanolamines results in amphiphilic modular metabolites (approximately 100 identified compounds) that are released into the environment and exhibit potential signaling functions. Exclusively male-produced β-sophorosyl N-acyl-phosphoethanolamines like SNAP-13:1cyclo retain females of Caenorhabditis wallacei and Caenorhabditis brenneri, and its biosynthesis requires bacterial cyclo fatty acids 17:1cyclo and 19:1cyclo, thereby translating growth phase-dependent bacterial lipogeneses into a behavioral signal. Amphiphilic 2-(β-glucosyl)-glyceryl N-eicosapentaenoyl phosphoethanolamine (GGp-NAE-20:5), a dominating component of the Caenorhabditis elegans metabolome, represents a water-soluble derivative of N-eicosapentaenoyl ethanolamine (NAE 20:5), potentially enabling intra- and interspecies endocannabinoid signaling.
期刊介绍:
ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.