Ascarosides and ascaroside esters in Ascaris lumbricoides (Nematoda)

Jezyk, Peter F.; Fairbairn, Donald

doi:10.1016/0010-406x(67)90334-9

Cited by 34 publications

(28 citation statements)

References 22 publications

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“…It is possible that these very lipophilic compounds constitute the substrates for the ␤-oxidation cascade producing ascarosides ascr#1 to ascr#8. Similar long-chained O-ascarylosyl-(2, -1)-alkanediols have been identified from several parasitic nematode species, where they occur in large quantities in the egg's internal lipid layer (22)(23)(24).…”

Section: Discussionmentioning

confidence: 61%

“…Chromatographic isolation of the ascarosides present in both daf-22 and wild-type extracts revealed highly lipophilic compounds featuring side chains of 29 and 31 carbon atoms, which are similar to lipids previously identified from egg shells of Ascaris sp. (see SI Appendix) (22)(23)(24). Thus, daf-22 metabolite extracts are distinguished from wild type by their lack of ascarosides with short side chains.…”

Section: Mass Spectrometric Validation Of Dans Resultsmentioning

confidence: 99%

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A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans

Pungaliya

Srinivasan

Fox

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

218

357

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Small molecule metabolites play important roles in Caenorhabditis elegans biology, but effective approaches for identifying their chemical structures are lacking. Recent studies revealed that a family of glycosides, the ascarosides, differentially regulate C. elegans development and behavior. Low concentrations of ascarosides attract males and thus appear to be part of the C. elegans sex pheromone, whereas higher concentrations induce developmental arrest at the dauer stage, an alternative, nonaging larval stage. The ascarosides act synergistically, which presented challenges for their identification via traditional activity-guided fractionation. As a result the chemical characterization of the dauer and male attracting pheromones remained incomplete. Here, we describe the identification of several additional pheromone components by using a recently developed NMR-spectroscopic approach, differential analysis by 2D NMR spectroscopy (DANS), which simplifies linking small molecule metabolites with their biological function. DANS-based comparison of wild-type C. elegans and a signaling-deficient mutant, daf-22, enabled identification of 3 known and 4 previously undescribed ascarosides, including a compound that features a p-aminobenzoic acid subunit. Biological testing of synthetic samples of these compounds revealed additional evidence for synergy and provided insights into structure-activity relationships. Using a combination of the three most active ascarosides allowed full reconstitution of the maleattracting activity of wild-type pheromone extract. Our results highlight the efficacy of DANS as a method for identifying smallmolecule metabolites and placing them within a specific genetic context. This study further supports the hypothesis that ascarosides represent a structurally diverse set of nematode signaling molecules regulating major life history traits.dauer formation ͉ differential analysis ͉ metabolomics ͉ NMR spectroscopy ͉ sex pheromone

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Section: Discussionmentioning

confidence: 61%

Section: Mass Spectrometric Validation Of Dans Resultsmentioning

confidence: 99%

A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans

Pungaliya

Srinivasan

Fox

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

218

357

View full text Add to dashboard Cite

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“…The presence of the long-chain ascarosides in the mutant strains may thus represent the accumulation of upstream intermediates in the dauer pheromone biosynthetic pathway. Interestingly, there is some evidence for the presence of very long-chain ascarosides in nematodes; they have been isolated from the internal lipid layer of the eggs of a range of nematode species (29,30), where they provide a highly resistant barrier that protects the eggs from chemical treatments (31,32). Typically, the side chains of these ascarosides are 32-34 carbons in length, and are either C-2 monols or C-2, -1 diols.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of the Caenorhabditis elegans dauer pheromone

Butcher

Ragains

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

150

193

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To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid ␤-oxidation. We also show that dhs-28, which encodes a homolog of the human D-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the shortchain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state. ascaroside ͉ daf-22 ͉ dhs-28

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“…Based on the structure of the side chain, they are classified as long-chain monool glycosides, diol monoglycosides and diol diglycosides [3]. Ascarosides of Ascaris are present in embryos, mainly in the form of esters of acetic, propylic, and isovaleric acids [2]. Upon fertilization, the ascarosides are deesterified and translocated to the inner layer of the newly formed eggshell, being a major constituent of this layer and providing eggshell impermeability [4].…”

mentioning

confidence: 99%

“…-Ascarosides, glycolipids containing the 3,6-dideoxysugar ascarylose (3,6-dideoxy-l-arabino-hexose), have been described in parasitic nematodes of the genus Ascaris, almost a century ago [1] [2]. Based on the structure of the side chain, they are classified as long-chain monool glycosides, diol monoglycosides and diol diglycosides [3].…”

mentioning

confidence: 99%