Comparative Metabolomics Reveals Biogenesis of Ascarosides

Frank Schroeder’s group recently published manuscript describes the use of an MS/MS-based screen to investigate a class of signaling molecules recently identified in the model organism C. elegans, the ascarosides. Schroeder and other groups have described about a dozen ascarosides and shown that these compounds act as regulators of highly conserved biological pathways, but many aspects of these compounds’ biogenesis remain unclear. Schroeder shows that the previously described ascarosides are merely the “tip of the iceberg”, representing examples for a structurally diverse library of small molecules derived from specific combinations of building blocks from three major metabolic pathways. Given their origin in an animal (as opposed to a microorganism), these compounds’ structural complexity and modular assembly is unexpected. Most of the compounds are produced at much lower concentrations than any previously identified ascarosides, and some are of extremely high biological potency. This paper demonstrates the utility of applying MS/MS-based comparative metabolomics to a series of mutant strains for characterizing the biosynthetic pathway of an unusual class of signaling molecules.

For more on the Schroeder Lab

Comparative Metabolomics: JACS 2012
http://pubs.acs.org/doi/abs/10.1021/ja210202y