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A Large Family of Enzymes Responsible for the Modular Architecture of Nematode Pheromones
journal contribution
posted on 2020-07-30, 19:44 authored by Nasser Faghih, Subhradeep Bhar, Yue Zhou, Abdul Rouf Dar, Kevin Mai, Laura S. Bailey, Kari B. Basso, Rebecca A. ButcherThe nematode Caenorhabditis
elegans produces a
broad family of pheromones, known as the ascarosides, that are modified
with a variety of groups derived from primary metabolism. These modifications
are essential for the diverse activities of the ascarosides in development
and various behaviors, including attraction, aggregation, avoidance,
and foraging. The mechanism by which these different groups are added
to the ascarosides is poorly understood. Here, we identify a family
of over 30 enzymes, which are homologous to mammalian carboxylesterase
(CES) enzymes, and show that a number of these enzymes are responsible
for the selective addition of specific modifications to the ascarosides.
Through stable isotope feeding experiments, we demonstrate the in vivo activity of the CES-like enzymes and provide direct
evidence that the acyl-CoA synthetase ACS-7, which was previously
implicated in the attachment of certain modifications to the ascarosides
in C. elegans, instead activates the side chains
of certain ascarosides for shortening through β-oxidation. Our
data provide a key to the combinatorial logic that gives rise to different
modified ascarosides, which should greatly facilitate the exploration
of the specific biological functions of these pheromones in the worm.