The nematode C. elegans uses small molecules to communicate with other worms and to control fundamental processes, such as development, metabolism, fertility, and lifespan, and various cooperative behaviors. This talk will describe our work on two important classes of natural products from C. elegans, the ascarosides and the nemamides. C. elegans secretes ascarosides, derivatives of the 3,6-dideoxysugar ascarylose, as pheromones to coordinate its development and behavior. We are using a multidisciplinary approach, including RNAi-based screens, metabolomics, in vitro enzyme assays, organic synthesis of biosynthetic intermediates, and X-ray crystallography, to study the ascaroside biosynthetic pathway. Our work has shown how peroxisomal β-oxidation is used to control the production of different ascaroside pheromones and how environmental conditions influence this process. In a second area of research, we have used comparative metabolomics and NMR spectroscopy to discover the first hybrid polyketide-nonribosomal peptides from an animal, the nemamides from C. elegans. We are using CRISPR-Cas9 and comparative metabolomics to explore the role of specific enzymatic domains in nemamide biosynthesis. Our work is providing insights into the biosynthesis of natural products in the context of a complex animal system.

Decoding the chemical signals of the worm

2019 Spring National Meeting

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