Biosynthesis of Modular Ascarosides in C. elegans
Oishika Panda
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorAllison E. Akagi
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Search for more papers by this authorDr. Alexander B. Artyukhin
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorDr. Joshua C. Judkins
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorHenry H. Le
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorDr. Parag Mahanti
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorSarah M. Cohen
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Search for more papers by this authorProf. Paul W. Sternberg
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Search for more papers by this authorCorresponding Author
Prof. Frank C. Schroeder
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorOishika Panda
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorAllison E. Akagi
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Search for more papers by this authorDr. Alexander B. Artyukhin
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorDr. Joshua C. Judkins
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorHenry H. Le
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorDr. Parag Mahanti
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorSarah M. Cohen
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Search for more papers by this authorProf. Paul W. Sternberg
Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Search for more papers by this authorCorresponding Author
Prof. Frank C. Schroeder
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA
Search for more papers by this authorGraphical Abstract
From the waste bin: C. elegans uses simple building blocks from primary metabolism to construct a modular library of signaling molecules, the ascarosides. It is demonstrated that lysosome-related organelles, which are essentially cellular waste-disposal centers, play a major role in the assembly of these compounds, which requires the activation of building blocks by a specific acyl-CoA synthetase.
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.
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