Dataset Information

Identification of Uric Acid Gluconucleoside-Ascaroside Conjugates in Caenorhabditis elegans by Combining Synthesis and MicroED.

ABSTRACT: Few nucleoside-derived natural products have been identified from animals, despite the ubiquity of nucleosides in living organisms. Here, we use a combination of synthesis and the emerging electron microscopy technique microcrystal electron diffraction to determine the structures of several N³-(β-glucopyranosyl)uric acid derivatives in Caenorhabditis elegans. These noncanonical gluconucleosides further integrate an ascaroside moiety, for which we present a shortened synthetic route. The production of a phosphorylated gluconucleoside is influenced by evolutionarily conserved insulin signaling.

SUBMITTER: Curtis BJ

PROVIDER: S-EPMC7526323 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Identification of Uric Acid Gluconucleoside-Ascaroside Conjugates in Caenorhabditis elegans by Combining Synthesis and MicroED.

Curtis Brian J BJ Kim Lee Joon LJ Wrobel Chester J J CJJ Eagan James M JM Smith Rubin A RA Burch Jessica E JE Le Henry H HH Artyukhin Alexander B AB Nelson Hosea M HM Schroeder Frank C FC

Organic letters 20200821 17

Few nucleoside-derived natural products have been identified from animals, despite the ubiquity of nucleosides in living organisms. Here, we use a combination of synthesis and the emerging electron microscopy technique microcrystal electron diffraction to determine the structures of several N3-(β-glucopyranosyl)uric acid derivatives in Caenorhabditis elegans. These noncanonical gluconucleosides further integrate an ascaroside moiety, for which we present a shortened synt ...[more]

PMID: 32820938

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Project description:BackgroundThe ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as "dauer pheromones" because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development.Methodology/principal findingsCultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions.Conclusions/significanceAscaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies.

Dataset Information

Identification of Uric Acid Gluconucleoside-Ascaroside Conjugates in Caenorhabditis elegans by Combining Synthesis and MicroED.

Publications

Identification of Uric Acid Gluconucleoside-Ascaroside Conjugates in <i>Caenorhabditis elegans</i> by Combining Synthesis and MicroED.

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