{"doi":"10.1093/genetics/163.2.545","title":"Short-Chain Fatty Acid Activation by Acyl-Coenzyme A Synthetases Requires SIR2 Protein Function in <i>Salmonella enterica</i> and <i>Saccharomyces cerevisiae</i>","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>SIR2 proteins have NAD+-dependent histone deacetylase activity, but no metabolic role has been assigned to any of these proteins. In Salmonella enterica, SIR2 function was required for activity of the acetyl-CoA synthetase (Acs) enzyme. A greater than two orders of magnitude increase in the specific activity of Acs enzyme synthesized by a sirtuin-deficient strain was measured after treatment with homogeneous S. enterica SIR2 protein. Human SIR2A and yeast SIR2 proteins restored growth of SIR2-deficient S. enterica on acetate and propionate, suggesting that eukaryotic cells may also use SIR2 proteins to control the synthesis of acetyl-CoA by the level of acetylation of acetyl-CoA synthetases. Consistent with this idea, growth of a quintuple sir2 hst1 hst2 hst3 hst4 mutant strain of the yeast Saccharomyces cerevisiae on acetate or propionate was severely impaired. The data suggest that the Hst3 and Hst4 proteins are the most important for allowing growth on these short-chain fatty acids.</jats:p>","journal":"Genetics","year":2003,"id":14695,"datarank":4.349320242789033,"base_score":4.68213122712422,"endowment":4.68213122712422,"self_citation_contribution":0.7023196840686331,"citation_network_contribution":3.6470005587204,"self_endowment_contribution":0.7023196840686331,"citer_contribution":3.6470005587204,"corpus_percentile":null,"corpus_rank":null,"citation_count":107,"citer_count":79,"citers_with_citation_signal":74,"citers_with_endowment":74,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":114984,"name":"Hidekazu Takahashi","orcid":null,"position":1,"is_corresponding":false},{"id":114985,"name":"Jef D Boeke","orcid":null,"position":2,"is_corresponding":false},{"id":114986,"name":"Jorge C Escalante-Semerena","orcid":null,"position":3,"is_corresponding":false},{"id":114983,"name":"Vincent J Starai","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.68213122712422,"endowment":4.68213122712422,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12618394","pmcid":"PMC1462443","openalex_id":"https://openalex.org/W2149630911","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM-62203","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM062203","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM-62385","title":null}],"total_grants":3,"fwci":6.4677,"citation_percentile":0.96095656,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":5},{"year":2014,"count":10},{"year":2015,"count":7},{"year":2016,"count":3},{"year":2017,"count":2},{"year":2018,"count":5},{"year":2019,"count":5},{"year":2020,"count":3},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"closed","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://academic.oup.com/genetics/article-pdf/163/2/545/42047161/genetics0545.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/genetics/163.2.545","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12618394","host_type":"repository"}],"fields_of_study":["Sirtuins and Resveratrol in Medicine","Endoplasmic Reticulum Stress and Disease","Autophagy in Disease and Therapy","Acetate Kinase","Acetates","Coenzyme A Ligases","Escherichia coli Proteins","Fatty Acids","Histone Deacetylases","Mutation","Phosphate Acetyltransferase","Phosphotransferases (Carboxyl Group Acceptor)","Propionates","Saccharomyces cerevisiae","Salmonella enterica","Silent Information Regulator Proteins, Saccharomyces cerevisiae","Sirtuin 2","Sirtuins"],"mesh_terms":["Acetate Kinase","Acetates","Coenzyme A Ligases","Fatty Acids","Histone Deacetylases","Mutation","Phosphate Acetyltransferase","Propionates","Saccharomyces cerevisiae","Phosphotransferases (Carboxyl Group Acceptor)","Salmonella enterica","Escherichia coli Proteins","Sirtuins","Silent Information Regulator Proteins, Saccharomyces cerevisiae","Sirtuin 2"],"keywords":["Salmonella enterica","Biology","Biochemistry","Acetylation","Saccharomyces cerevisiae","Sirtuin","NAD+ kinase","Enzyme","SIRT3","Acetyl-CoA","Propionate","SIRT2","Yeast","Gene","Escherichia coli"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T13:49:03.537540Z","pmid":null,"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":[]}