Biosynthesis of Modular Ascarosides in C. elegans
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.
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.Attached Files
Supplemental Material - anie201700103-sup-0001-misc_information.pdf
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Additional details
- PMCID
- PMC5486983
- Eprint ID
- 76471
- Resolver ID
- CaltechAUTHORS:20170410-105746372
- National BioResource Project
- NIH
- P40 OD010440
- NIH
- GM113692
- NIH
- GM088290
- NIH Predoctoral Fellowship
- T32-GM007616
- NIH Predoctoral Fellowship
- T32 GM008500
- NSF
- DBI-0618969
- Howard Hughes Medical Institute (HHMI)
- Created
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2017-04-10Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field