Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis

Abstract

In the nematodes Caenorhabditis elegans and Pristionchus pacificus, a modular library of small molecules control behavior, lifespan, and development. However, little is known about the final steps of their biosynthesis, in which diverse building blocks from primary metabolism are attached to glycosides of the dideoxysugar ascarylose, the ascarosides. We combine metabolomic analysis of natural isolates of Ppacificuswith genome-wide association mapping to identify a putative carboxylesterasePpa-uar-1, that is required for attachment of a pyrimidine-derived moiety in the biosynthesis of ubas#1, a major dauer pheromone component. Comparative metabolomic analysis of wild-type and Ppa-uar-1 mutants showed that Ppa-uar-1 is required specifically for the biosynthesis of ubas#1 and related metabolites. Heterologous expression of Ppa-UAR-1 in Celegans yielded a non-endogenous ascaroside, whose structure confirmed that Ppa-uar-1 is involved in modification of a specific position in ascarosides. Our study demonstrates the utility of natural variation-based approaches for uncovering biosynthetic pathways.

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Titel Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis
Medien Cell Chemical Biology
Verlag ---
Heft 6
Band 25
ISBN ---
Verfasser/Herausgeber Jan M. Falcke, Neelanjan Bose, Alexander B. Artyukhin, Christian Rödelsperger, Gabriel V. Markov, Joshua J. Yim, Prof. Dr. Dominik Grimm, Marc H. Claassen, Oishika Panda, Joshua A. Baccile, Ying K. Zhang, Henry H. Le, Dino Jolic, Frank C. Schroeder, Ralf J. Sommer
Seiten 787-796
Veröffentlichungsdatum 21.06.2018
Projekttitel ---
Zitation Falcke, J.; Bose, N.; Artyukhin, A.; Rödelsperger, C.; Markov, G.; Yim, J.; Grimm, D.; Claassen, M.; Panda, O.; Baccile, J.; Zhang, Y.; Le, H.; Jolic, D.; Schroeder, F.; Sommer, R. (2018): Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis. Cell Chemical Biology 25 (6), S. 787-796. DOI: 10.1016/j.chembiol.2018.04.004