{"doi":"10.1021/acssynbio.3c00570","title":"Improvement of Chalcone Synthase Activity and High-Efficiency Fermentative Production of (2<i>S</i>)-Naringenin via <i>In Vivo</i> Biosensor-Guided Directed Evolution","abstract":null,"journal":"ACS Synthetic Biology","year":2024,"id":674622,"datarank":0.4887144807032224,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.0,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":36624,"name":"Ning Li","orcid":"0000-0002-6368-8194","position":1,"is_corresponding":false},{"id":1553456,"name":"Shenghu Zhou","orcid":"0000-0002-7058-430X","position":2,"is_corresponding":false},{"id":1418170,"name":"Liang Zhang","orcid":"0000-0001-6596-7691","position":3,"is_corresponding":false},{"id":342062,"name":"Sha Xu","orcid":"0000-0001-8987-4940","position":4,"is_corresponding":false},{"id":180004,"name":"Jingwen Zhou","orcid":"0000-0002-3949-3733","position":5,"is_corresponding":false},{"id":180000,"name":"Yingjia Tong","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Improvement of Chalcone Synthase Activity and High-Efficiency Fermentative Production of (2<i>S</i>)-Naringenin via <i>In Vivo</i> Biosensor-Guided Directed Evolution","abstract":"Chalcone synthase (CHS) catalyzes the rate-limiting step of (2<i>S</i>)-naringenin (the essential flavonoid skeleton) biosynthesis. Improving the activity of the CHS by protein engineering enhances (2<i>S</i>)-naringenin production by microbial fermentation and can facilitate the production of valuable flavonoids. A (2<i>S</i>)-naringenin biosensor based on the TtgR operon was constructed in <i>Escherichia coli</i> and its detection range was expanded by promoter optimization to 0-300 mg/L, the widest range for (2<i>S</i>)-naringenin reported. The high-throughput screening scheme for CHS was established based on this biosensor. A mutant, <i>Sj</i>CHS1<sup>S208N</sup> with a 2.34-fold increase in catalytic activity, was discovered by directed evolution and saturation mutagenesis. A pathway for <i>de novo</i> biosynthesis of (2<i>S</i>)-naringenin by <i>Sj</i>CHS1<sup>S208N</sup> was constructed in <i>Saccharomyces cerevisiae</i>, combined with CHS precursor pathway optimization, increasing the (2<i>S</i>)-naringenin titer by 65.34% compared with the original strain. Fed-batch fermentation increased the titer of (2<i>S</i>)-naringenin to 2513 ± 105 mg/L, the highest reported so far. These findings will facilitate efficient flavonoid biosynthesis and further modification of the CHS in the future.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38662928","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFA0911500","title":null},{"funder_name":"China Postdoctoral Science Foundation","grant_id":"2019M651701","title":null},{"funder_name":"National Science Fund for Distinguished Young Scholars","grant_id":"21822806","title":null},{"funder_name":"Wuxi Municipal Bureau on Science and Technology","grant_id":"K20231042","title":null},{"funder_name":"Fundamental Research Funds for the Central Universities","grant_id":"JUSRP123043","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"21908078","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"32021005","title":null}],"total_grants":7,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"https://doi.org/10.15223/policy-029","oa_locations":[{"url":"https://pubs.acs.org/doi/pdf/10.1021/acssynbio.3c00570","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Escherichia coli","Saccharomyces cerevisiae","Flavanones","Acyltransferases","Directed Molecular Evolution","Protein Engineering","Biosensing Techniques","Fermentation","Operon","Promoter Regions, Genetic","Metabolic Engineering"],"keywords":["Biosensor","Flavonoids","Directed evolution","chalcone synthase","(2S)-naringenin"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T17:35:09.293227Z","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":[]}