« Previous AbstractDevelopmental Exposure to Environmental Toxicants    Next AbstractExoskeleton formation in Apis mellifera: cuticular hydrocarbons profiles and expression of desaturase and elongase genes during pupal and adult development »

Cell Chem Biol

Title:		Linking Genomic and Metabolomic Natural Variation Uncovers Nematode Pheromone Biosynthesis
Author(s):		Falcke JM; Bose N; Artyukhin AB; Rodelsperger C; Markov GV; Yim JJ; Grimm D; Claassen MH; Panda O; Baccile JA; Zhang YK; Le HH; Jolic D; Schroeder FC; Sommer RJ;
Address:		"Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany. Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany; Sorbonne Universites, UPMC Univ Paris 06, CNRS, UMR 8227 Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff, France. Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. Machine Learning and Computational Biology Research Group, Max Planck Institute for Intelligent Systems, 72076 Tubingen, Germany. Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address: fs31@cornell.edu. Department for Evolutionary Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany. Electronic address: ralf.sommer@tuebingen.mpg.de"
Journal Title:		Cell Chem Biol
Year:		2018
Volume:		20180517
Issue:		6
Page Number:		787 - 796
DOI:		10.1016/j.chembiol.2018.04.004
ISSN/ISBN:		2451-9448 (Electronic) 2451-9456 (Print) 2451-9448 (Linking)
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"
Keywords:		Animals Carboxylic Ester Hydrolases/genetics/metabolism *Genomics *Metabolomics Nematoda/*genetics/*metabolism Pheromones/*biosynthesis/chemistry/*genetics Caenorhabditis elegans Gwas Pristionchus pacificus ascarosides biosynthesis carboxylesterase dauer;
Notes:		"MedlineFalcke, Jan M Bose, Neelanjan Artyukhin, Alexander B Rodelsperger, 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 eng R01 GM088290/GM/NIGMS NIH HHS/ R01 GM113692/GM/NIGMS NIH HHS/ T32 GM008500/GM/NIGMS NIH HHS/ HHMI/Howard Hughes Medical Institute/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2018/05/22 Cell Chem Biol. 2018 Jun 21; 25(6):787-796.e12. doi: 10.1016/j.chembiol.2018.04.004. Epub 2018 May 17"