{"doi":"10.1039/d5sc01027f","title":"Biochemical dissection of a fungal highly reducing polyketide synthase condensing region reveals basis for acyl group selection","abstract":"reconstitution of each catalytic step carried out by a hrPKS condensing region. Application of intact protein mass spectrometry shows that the AT domain operates selective acyl transfer to the ACP domain, ensuring precise loading of the coenzyme A (CoA)-tethered acetyl and malonyl starter/extender units, which is governed by a substrate recycling mechanism and kinetic parameters towards each substrate. The KS domain is shown to select for the correct starter unit for transacylation and subsequent chain elongation, and was also able to utilise methylmalonyl-CoA. This work provides the first comprehensive interrogation of a fungal hrPKS condensing region, which both affirms and expands our understanding of how these systems function, and provides a framework for future bioengineering efforts.","journal":"Chemical Science","year":2025,"id":516728,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1359752,"name":"Nazia Auckloo","orcid":"0000-0002-0851-4407","position":1,"is_corresponding":false},{"id":1359753,"name":"Ying-Ning Ho","orcid":"0000-0002-8520-9801","position":2,"is_corresponding":false},{"id":1222750,"name":"Shaonan Liu","orcid":"0009-0001-7864-9534","position":3,"is_corresponding":false},{"id":476923,"name":"Yang Hai","orcid":"0000-0002-2039-5367","position":4,"is_corresponding":false},{"id":476924,"name":"Matthew Jenner","orcid":"0000-0003-2317-3011","position":5,"is_corresponding":false},{"id":1258868,"name":"Mia E. Foran","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"40584239","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":[]}