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Biosynthesis of Modular Ascarosides in C. elegans

Panda, Oishika and Akagi, Allison E. and Artyukhin, Alexander B. and Judkins, Joshua C. and Le, Henry H. and Mahanti, Parag and Cohen, Sarah M. and Sternberg, Paul W. and Schroeder, Frank C. (2017) Biosynthesis of Modular Ascarosides in C. elegans. Angewandte Chemie International Edition, 56 (17). pp. 4729-4733. ISSN 1433-7851. PMCID PMC5486983. https://resolver.caltech.edu/CaltechAUTHORS:20170410-105746372

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Abstract

The nematode Caenorhabditis elegans uses simple building blocks from primary metabolism and a strategy of modular assembly to build a great diversity of signaling molecules, the ascarosides, which function as a chemical language in this model organism. In the ascarosides, the dideoxysugar ascarylose serves as a scaffold to which diverse moieties from lipid, amino acid, neurotransmitter, and nucleoside metabolism are attached. However, the mechanisms that underlie the highly specific assembly of ascarosides are not understood. We show that the acyl-CoA synthetase ACS-7, which localizes to lysosome-related organelles, is specifically required for the attachment of different building blocks to the 4′-position of ascr#9. We further show that mutants lacking lysosome-related organelles are defective in the production of all 4′-modified ascarosides, thus identifying the waste disposal system of the cell as a hotspot for ascaroside biosynthesis.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/anie.201700103DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/anie.201700103/abstractPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486983/PubMed CentralArticle
ORCID:
AuthorORCID
Akagi, Allison E.0000-0002-7233-6190
Sternberg, Paul W.0000-0002-7699-0173
Schroeder, Frank C.0000-0002-4420-0237
Additional Information:© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Manuscript received: January 4, 2017; Revised: February 20, 2017; Final Article published: March 28, 2017. Strains used in this work were provided by NBRP (Japan) and CGC which is funded by NIH (P40 OD010440). This work was supported in part by the NIH (GM113692, GM088290 to F.C.S., T32-GM007616 to A.A., T32 GM008500 to J.C.J.), NSF (DBI-0618969 to BTI), and HHMI. The authors declare no conflict of interest.
Funders:
Funding AgencyGrant Number
National BioResource ProjectUNSPECIFIED
NIHP40 OD010440
NIHGM113692
NIHGM088290
NIH Predoctoral FellowshipT32-GM007616
NIH Predoctoral FellowshipT32 GM008500
NSFDBI-0618969
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:17
PubMed Central ID:PMC5486983
Record Number:CaltechAUTHORS:20170410-105746372
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170410-105746372
Official Citation:O. Panda, A. E. Akagi, A. B. Artyukhin, J. C. Judkins, H. H. Le, P. Mahanti, S. M. Cohen, P. W. Sternberg, F. C. Schroeder, Angew. Chem. Int. Ed. 2017, 56, 4729
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76471
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Apr 2017 18:11
Last Modified:03 Oct 2019 17:01

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