{"doi":"10.1021/jacs.1c05908","title":"Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates <i>C. elegans</i> Starvation Survival","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.","journal":"Journal of the American Chemical Society","year":2021,"id":178702,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":339573,"name":"Jingfang Yu","orcid":"0000-0003-1770-5368","position":1,"is_corresponding":false},{"id":339578,"name":"Pedro R. Rodrigues","orcid":"0000-0002-1539-3017","position":2,"is_corresponding":false},{"id":725212,"name":"Andreas H. Ludewig","orcid":null,"position":3,"is_corresponding":false},{"id":339576,"name":"Brian J. Curtis","orcid":"0000-0001-7503-3403","position":4,"is_corresponding":false},{"id":339572,"name":"Sarah M Cohen","orcid":"0000-0003-4469-2670","position":5,"is_corresponding":false},{"id":352621,"name":"Bennett W. Fox","orcid":"0000-0002-9749-3491","position":6,"is_corresponding":false},{"id":724652,"name":"Michael P. O’Donnell","orcid":"0000-0001-8313-8969","position":7,"is_corresponding":false},{"id":49667,"name":"Paul W. Sternberg","orcid":"0000-0002-7699-0173","position":8,"is_corresponding":false},{"id":72618,"name":"Frank C. Schroeder","orcid":"0000-0002-4420-0237","position":9,"is_corresponding":false},{"id":339571,"name":"Chester J. J. Wrobel","orcid":"0000-0001-6047-4644","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:47:40.592580Z","pmid":"34460264","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}