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Repurposing degradation pathways for modular metabolite biosynthesis in nematodes.
Chester J J Wrobel1, Frank C Schroeder2
1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Nature Chemical Biology
|April 6, 2023
Summary
Nematodes create complex signaling molecules called modular metabolites by combining building blocks from various metabolic pathways. This novel biosynthesis strategy, mediated by carboxylesterases, expands our understanding of nematode chemical diversity.
Area of Science:
- Biochemistry
- Molecular Biology
- Nematology
Background:
- Nematodes utilize building blocks from metabolic degradation for complex molecule synthesis.
- These molecules, including ascarosides and glucosides, have diverse signaling functions.
Purpose of the Study:
- To investigate the biosynthesis and enzymatic mechanisms of modular metabolites in nematodes.
- To explore the origin and diversity of these compounds, potentially uncovering new metabolic pathways.
Main Methods:
- Utilized untargeted metabolomics for rapid compound discovery.
- Employed genome-wide association studies to identify key enzymes (carboxylesterases).
- Analyzed metabolic pathways involved in neurotransmitter, amino acid, nucleoside, and fatty acid metabolism.
Main Results:
- Identified hundreds of modular ascarosides and glucosides assembled from various metabolic precursors.
- Carboxylesterases were confirmed as key enzymes in the modular assembly process.
- Demonstrated that modular metabolite biosynthesis involves repurposing of detoxification mechanisms.
Conclusions:
- Modular metabolites represent a unique nematode biosynthetic strategy for generating structural and functional diversity.
- This discovery highlights the synergy between phenotype-driven discovery, metabolomics, and genomics in annotating 'metabolic dark matter'.
- Further research is needed to fully elucidate the biosynthesis and functions of these compounds.
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