{"doi":"10.1126/science.adj7621","title":"Evolution-guided engineering of <i>trans</i> -acyltransferase polyketide synthases","abstract":"Bacterial multimodular polyketide synthases (PKSs) are giant enzymes that generate a wide range of therapeutically important but synthetically challenging natural products. Diversification of polyketide structures can be achieved by engineering these enzymes. However, notwithstanding successes made with textbook cis -acyltransferase ( cis -AT) PKSs, tailoring such large assembly lines remains challenging. Unlike textbook PKSs, trans -AT PKSs feature an extraordinary diversity of PKS modules and commonly evolve to form hybrid PKSs. In this study, we analyzed amino acid coevolution to identify a common module site that yields functional PKSs. We used this site to insert and delete diverse PKS parts and create 22 engineered trans -AT PKSs from various pathways and in two bacterial producers. The high success rates of our engineering approach highlight the broader applicability to generate complex designer polyketides.","journal":"Science","year":2024,"id":417891,"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":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1014147,"name":"Stefan Leopold‐Messer","orcid":"0000-0003-3490-3550","position":1,"is_corresponding":false},{"id":1204506,"name":"Hannah A. Minas","orcid":"0000-0003-2997-6915","position":2,"is_corresponding":false},{"id":1204507,"name":"Clara Chepkirui","orcid":"0000-0001-5469-4106","position":3,"is_corresponding":false},{"id":1204508,"name":"Pornsuda Chawengrum","orcid":"0009-0007-3493-0344","position":4,"is_corresponding":false},{"id":1204509,"name":"Silke Reiter","orcid":"0009-0002-7232-8147","position":5,"is_corresponding":false},{"id":1204510,"name":"Roy A. Meoded","orcid":"0000-0002-5139-1676","position":6,"is_corresponding":false},{"id":1204511,"name":"Sarah Wolf","orcid":"0009-0009-2319-7735","position":7,"is_corresponding":false},{"id":1204512,"name":"Ferdinand Genz","orcid":"0009-0002-4868-2752","position":8,"is_corresponding":false},{"id":1204513,"name":"Nancy Magnus","orcid":"0009-0006-9106-3147","position":9,"is_corresponding":false},{"id":1204514,"name":"Birgit Piechulla","orcid":"0000-0002-3130-3018","position":10,"is_corresponding":false},{"id":264498,"name":"Allison S. Walker","orcid":"0000-0001-5666-7232","position":11,"is_corresponding":false},{"id":392241,"name":"Jörn Piel","orcid":"0000-0002-2282-8154","position":12,"is_corresponding":false},{"id":1204505,"name":"Mathijs F. J. Mabesoone","orcid":"0000-0003-1314-7215","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T01:56:56.807779Z","pmid":"38513027","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":[]}