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Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis.
Falcke, Jan M; Bose, Neelanjan; Artyukhin, Alexander B; Rödelsperger, Christian; Markov, Gabriel V; Yim, Joshua J; Grimm, Dominik; Claassen, Marc H; Panda, Oishika; Baccile, Joshua A; Zhang, Ying K; Le, Henry H; Jolic, Dino; Schroeder, Frank C; Sommer, Ralf J.
Afiliación
  • Falcke JM; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
  • Bose N; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Artyukhin AB; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Rödelsperger C; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
  • Markov GV; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany; Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8227 Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff, France.
  • Yim JJ; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Grimm D; Machine Learning and Computational Biology Research Group, Max Planck Institute for Intelligent Systems, 72076 Tübingen, Germany.
  • Claassen MH; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
  • Panda O; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Baccile JA; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Zhang YK; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Le HH; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
  • Jolic D; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
  • Schroeder FC; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address: fs31@cornell.edu.
  • Sommer RJ; Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany. Electronic address: ralf.sommer@tuebingen.mpg.de.
Cell Chem Biol ; 25(6): 787-796.e12, 2018 06 21.
Article en En | MEDLINE | ID: mdl-29779955
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Feromonas / Genómica / Metabolómica / Nematodos Límite: Animals Idioma: En Revista: Cell Chem Biol Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Feromonas / Genómica / Metabolómica / Nematodos Límite: Animals Idioma: En Revista: Cell Chem Biol Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos