[
ACS Chem Biol,
2006]
Whereas the C. elegans genome was sequenced many years ago, the role of small molecule signals in its biology is still poorly understood. A recent publication reports the identification of two steroidal signaling molecules that regulate C. elegans reproductive development and dauer diapause via the nuclear receptor DAF-12. The two compounds, named dafachronic acids, represent the first endogenous ligands identified for any of the 284 nuclear receptors in C. elegans .
[
Chem Biol,
2015]
The metabolome of the nematode Caenorhabditis elegans, like that of other model organisms, remained largely uncharacterized until recent studies demonstrated the importance of small molecule-based signaling cascades for many aspects of nematode biology. These studies revealed that nematodes are amazingly skilled chemists: using simple building blocks from primary metabolism and a strategy of modular assembly, nematodes create complex molecular architectures that serve as signaling molecules. These nematode-derived modular metabolites (NDMMs) are based on the dideoxysugars ascarylose and paratose, which serve as scaffolds for the attachment of moieties from lipid, amino acid, neurotransmitter, and nucleoside metabolism. Although preliminary biosynthetic studies have confirmed the primary metabolism origin of some of the building blocks incorporated into NDMMs, the mechanisms that underlie their highly specific assembly are not understood. I argue that identification of new variants of primary metabolism-derived structures that serve important signaling functions in C. elegans and other nematodes provides a strong incentive for a comprehensive reanalysis of metabolism in higher animals, including humans.