{"doi":"10.1021/acs.biochem.2c00094","title":"Control of Unsaturation in <i>De Novo</i> Fatty Acid Biosynthesis by FabA","abstract":"Carrier protein-dependent biosynthesis provides a thiotemplated format for the production of natural products. Within these pathways, many reactions display exquisite substrate selectivity, a regulatory framework proposed to be controlled by protein–protein interactions (PPIs). In Escherichia coli, unsaturated fatty acids are generated within the de novo fatty acid synthase by a chain length-specific interaction between the acyl carrier protein AcpP and the isomerizing dehydratase FabA. To evaluate PPI-based control of reactivity, interactions of FabA with AcpP bearing multiple sequestered substrates were analyzed through NMR titration and guided high-resolution docking. Through a combination of quantitative binding constants, residue-specific perturbation analysis, and high-resolution docking, a model for substrate control via PPIs has been developed. The in silico results illuminate the mechanism of FabA substrate selectivity and provide a structural rationale with atomic detail. Helix III positioning in AcpP communicates sequestered chain length identity recognized by FabA, demonstrating a powerful strategy to regulate activity by allosteric control. These studies broadly illuminate carrier protein-dependent pathways and offer an important consideration for future inhibitor design and pathway engineering.","journal":"Biochemistry","year":2022,"id":291850,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":551861,"name":"Terra Sztain","orcid":"0000-0002-1327-8541","position":1,"is_corresponding":false},{"id":578675,"name":"Megan A. Young","orcid":"0000-0002-3330-3580","position":2,"is_corresponding":false},{"id":272018,"name":"D. John Lee","orcid":"0000-0002-5132-3243","position":3,"is_corresponding":false},{"id":295588,"name":"Tony D. Davis","orcid":"0000-0001-5629-7075","position":4,"is_corresponding":false},{"id":307460,"name":"Ruben Abagyan","orcid":"0000-0001-9309-2976","position":5,"is_corresponding":false},{"id":295592,"name":"Michael D. Burkart","orcid":"0000-0002-4472-2254","position":6,"is_corresponding":false},{"id":296917,"name":"Thomas G. Bartholow","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:30:42.221508Z","pmid":"35255690","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":[]}