Biosynthesis of the Caenorhabditis elegans dauer pheromone.
To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human d-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state.
Butcher
Rebecca A
RA
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Ragains
Justin R
JR
Li
Weiqing
W
Ruvkun
Gary
G
Clardy
Jon
J
Mak
Ho Yi
HY
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D053858:Metabolic Networks and Pathways; D010084:Oxidation-Reduction; D010675:Pheromones / Q000096:biosynthesis*; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D005227:Fatty Acids; D010675:Pheromones; C072087:sterol carrier proteins