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Biosynthesis of Modular Ascarosides in C. elegans
Oishika Panda1, Allison E Akagi2, Alexander B Artyukhin1
1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Angewandte Chemie (International Ed. in English)
|April 4, 2017
Summary
The nematode Caenorhabditis elegans assembles diverse signaling molecules called ascarosides. The acyl-CoA synthetase ACS-7 is crucial for attaching building blocks to ascarosides, with lysosome-related organelles acting as biosynthesis hotspots.
Area of Science:
- Molecular biology
- Biochemistry
- Cell biology
Background:
- The nematode Caenorhabditis elegans utilizes ascarosides, derived from primary metabolism, as a complex chemical language.
- Ascarosides are assembled modularly, with the dideoxysugar ascarylose serving as a scaffold for diverse metabolic moieties.
- The precise mechanisms governing the specific assembly of ascarosides remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the specific assembly of ascaroside signaling molecules.
- To identify the cellular components and pathways involved in ascaroside biosynthesis.
Main Methods:
- Investigated the role of acyl-CoA synthetase ACS-7 in ascaroside modification.
- Utilized genetic mutants lacking lysosome-related organelles to study ascaroside production.
- Analyzed the attachment of various building blocks to the 4'-position of ascarosides.
Main Results:
- The acyl-CoA synthetase ACS-7, localized in lysosome-related organelles, is essential for attaching specific building blocks to the 4'-position of ascaroside ascr#9.
- Mutants deficient in lysosome-related organelles exhibit defects in the production of all 4'-modified ascarosides.
- Lysosome-related organelles are identified as critical sites for ascaroside biosynthesis.
Conclusions:
- The study identifies ACS-7 as a key enzyme in the specific modification of ascarosides.
- Lysosome-related organelles, typically associated with waste disposal, play a significant role in the biosynthesis of signaling molecules.
- This research highlights the unexpected involvement of cellular waste management systems in the production of chemical communication molecules.