posted on 2021-08-30, 20:32authored byChester
J. J. Wrobel, Jingfang Yu, Pedro R. Rodrigues, Andreas H. Ludewig, Brian J. Curtis, Sarah M. Cohen, Bennett W. Fox, Michael P. O’Donnell, Paul W. Sternberg, Frank C. Schroeder
The recently discovered modular glucosides (MOGLs) form a large metabolite
library derived from combinatorial
assembly of moieties from amino acid, neurotransmitter, and lipid
metabolism in the model organism C. elegans. Combining
CRISPR-Cas9 genome editing, comparative metabolomics, and synthesis,
we show that the carboxylesterase homologue Cel-CEST-1.2 is responsible
for specific 2-O-acylation of diverse glucose scaffolds
with a wide variety of building blocks, resulting in more than 150
different MOGLs. We further show that this biosynthetic role is conserved
for the closest homologue of Cel-CEST-1.2 in the related nematode
species C. briggsae, Cbr-CEST-2. Expression of Cel-cest-1.2 and MOGL biosynthesis are strongly induced
by starvation conditions in C. elegans, one of the
premier model systems for mechanisms connecting nutrition and physiology. Cel-cest-1.2-deletion results in early death of adult animals
under starvation conditions, providing first insights into the biological
functions of MOGLs.