Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis.
Cell Chem Biol
; 25(6): 787-796.e12, 2018 06 21.
Article
de En
| MEDLINE
| ID: mdl-29779955
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 P. pacificus with genome-wide association mapping to identify a putative carboxylesterase, Ppa-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 C. elegans 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Phéromones
/
Génomique
/
Métabolomique
/
Nematoda
Limites:
Animals
Langue:
En
Journal:
Cell Chem Biol
Année:
2018
Type de document:
Article
Pays d'affiliation:
Allemagne