{"doi":"10.1021/acschembio.3c00596","title":"Algal Kainoid Synthases Exhibit Substrate-Dependent Hydroxylation and Cyclization Activities","abstract":"High Resolution Image Download MS PowerPoint Slide Fe II /α-ketoglutarate-dependent dioxygenases (Fe/αKG) make up a large enzyme family that functionalize C–H bonds on diverse organic substrates. Although Fe/αKG homologues catalyze an array of chemically useful reactions, hydroxylation typically predominates. Microalgal DabC uniquely forms a novel C–C bond to construct the bioactive pyrrolidine ring in domoic acid biosynthesis; however, we have identified that this kainoid synthase exclusively performs a stereospecific hydroxylation reaction on its cis substrate regioisomer. Mechanistic and kinetic analyses with native and alternative substrates identified a 20-fold rate increase in DabC radical cyclization over β-hydroxylation with no observable 1,5-hydrogen atom transfer. Moreover, this dual activity was conserved among macroalgal RadC1 and KabC homologues and provided insight into substrate recognition and reactivity trends. Investigation of this substrate-dependent chemistry improves our understanding of kainoid synthases and their biocatalytic application.","journal":"ACS Chemical Biology","year":2023,"id":337813,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":305305,"name":"Shaun M. K. McKinnie","orcid":"0000-0001-6776-6455","position":1,"is_corresponding":false},{"id":1069769,"name":"Austin Hopiavuori","orcid":"0000-0002-7093-7558","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T01:10:31.133446Z","pmid":"38047879","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":[]}