Modular metabolite assembly in C. elegans lysosome-related organelles

Le, H. H.; Wrobel, C. J.; Cohen, S. M.; Yu, J.; Park, H.; Helf, M. J.; Curtis, B. J.; Rodrigues, P. R.; Sternberg, P. W.; Schroeder, F. C.

doi:10.1101/2020.08.22.262956

bioRxiv · 10.1101/2020.08.22.262956

Modular metabolite assembly in C. elegans lysosome-related organelles

Le, H. H.·Wrobel, C. J.·Cohen, S. M.·Yu, J.·Park, H.·Helf, M. J.·Curtis, B. J.·Rodrigues, P. R.·Sternberg, P. W.·Schroeder, F. C.

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Abstract

Signaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/262956v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@6e83cborg.highwire.dtl.DTLVardef@18e9302org.highwire.dtl.DTLVardef@1557670org.highwire.dtl.DTLVardef@1d2ca50_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Le, H. H., Wrobel, C. J., Cohen, S. M., Yu, J., Park, H., Helf, M. J., Curtis, B. J., Rodrigues, P. R., Sternberg, P. W., Schroeder, F. C.. 2020-08-24. Modular metabolite assembly in C. elegans lysosome-related organelles. https://doi.org/10.1101/2020.08.22.262956

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