Modular Assembly of Primary Metabolic Building Blocks: A Chemical Language in C. elegans

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.