Comparative Ascaroside Profiling of Caenorhabditis Exometabolomes Reveals Species-Specific (ω) and (ω - 2)-Hydroxylation Downstream of Peroxisomal β-Oxidation

  • J Org Chem. 2018 Jul 6;83(13):7109-7120. doi: 10.1021/acs.joc.8b00094.
Chuanfu Dong  1  2 ,  Douglas K Reilly  3 ,  Célia Bergame  4 ,  Franziska Dolke  1 ,  Jagan Srinivasan  3 ,  Stephan H von Reuss  1  4
Affiliations
  • 1. Department of Bioorganic Chemistry , Max Planck Institute for Chemical Ecology , Hans-Knoell Strasse 8 , D-07745 Jena , Germany.
  • 2. Department for Integrative Evolutionary Biology , Max Planck Institute for Developmental Biology , Max-Planck-Ring 9 , D-72076 Tübingen , Germany.
  • 3. Department of Biology and Biotechnology , Worcester Polytechnic Institute , 60 Prescott Street , Worcester , Massachusetts 01605 , United States.
  • 4. Laboratory of Bioanalytical Chemistry , University of Neuchatel , Avenue de Bellevaux 51 , CH-2000 Neuchâtel , Switzerland.
PMID: 29480728 DOI: 10.1021/acs.joc.8b00094
Abstract

Chemical communication in nematodes such as the model organism Caenorhabditis elegans is modulated by a variety of glycosides based on the dideoxysugar l-ascarylose. Comparative ascaroside profiling of nematode exometabolome extracts using a GC-EIMS screen reveals that several basic components including ascr#1 (asc-C7), ascr#2 (asc-C6-MK), ascr#3 (asc-ΔC9), ascr#5 (asc-ωC3), and ascr#10 (asc-C9) are highly conserved among the Caenorhabditis. Three novel side chain hydroxylated ascaroside derivatives were exclusively detected in the distantly related C. nigoni and C. afra. Molecular structures of these species-specific putative signaling molecules were elucidated by NMR spectroscopy and confirmed by total synthesis and chemical correlations. Biological activities were evaluated using attraction assays. The identification of (ω)- and (ω - 2)-hydroxyacyl ascarosides demonstrates how GC-EIMS-based ascaroside profiling facilitates the detection of novel ascaroside components and exemplifies how species-specific hydroxylation of ascaroside aglycones downstream of peroxisomal β-oxidation increases the structural diversity of this highly conserved class of nematode signaling molecules.

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