| Literature DB >> 34460264 |
Chester J J Wrobel1, Jingfang Yu1, Pedro R Rodrigues1, Andreas H Ludewig1, Brian J Curtis1, Sarah M Cohen2, Bennett W Fox1, Michael P O'Donnell3, Paul W Sternberg2, Frank C Schroeder1.
Abstract
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.Entities:
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Year: 2021 PMID： 34460264 PMCID： PMC8594405 DOI： 10.1021/jacs.1c05908
Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 16.383