{"doi":"10.1021/jacs.4c16271","title":"O <sub>2</sub> Activation and Enzymatic C–H Bond Activation Mediated by a Dimanganese Cofactor","abstract":"Dioxygen (O 2 ) is a potent oxidant used by aerobic organisms for energy transduction and critical biosynthetic processes. Numerous metalloenzymes harness O 2 to mediate C–H bond hydroxylation reactions, but most commonly feature iron or copper ions in their active site cofactors. In contrast, many manganese-activated enzymes─such as glutamine synthetase and isocitrate lyase─perform redox neutral chemical transformations and very few are known to activate O 2 or C–H bonds. Here, we report that the dimanganese-metalated form of the cambialistic monooxygenase SfbO (Mn 2 –SfbO) can efficiently mediate enzymatic C–H bond hydroxylation. The activity of the dimanganese form of SfbO toward substrate hydroxylation is comparable to that of its heterobimetallic Mn/Fe form but exhibits distinct kinetic profiles. Kinetic, spectroscopic, and structural studies invoke a mixed-valent dimanganese cofactor (Mn II Mn III ) in O 2 activation and evidence a stoichiometric role for superoxide in maturing an O 2 -inert Mn II 2 cofactor. Computational studies support a hypothesis wherein superoxide addition to the Mn II 2 cofactor installs a critical bridging hydroxide ligand that stabilizes higher-valent manganese oxidation states. These findings establish the viability of proteinaceous dimanganese cofactors in mediating complex, multistep redox transformations.","journal":"Journal of the American Chemical Society","year":2025,"id":529682,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"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":334946,"name":"Guodong Rao","orcid":"0000-0001-8043-3436","position":1,"is_corresponding":false},{"id":417467,"name":"Jessica Nguyen","orcid":"0009-0007-4956-0702","position":2,"is_corresponding":false},{"id":334945,"name":"R. David Britt","orcid":"0000-0003-0889-8436","position":3,"is_corresponding":false},{"id":691101,"name":"Jonathan Rittle","orcid":"0000-0001-6241-6253","position":4,"is_corresponding":false},{"id":1237596,"name":"Chang Liu","orcid":"0000-0002-9393-101X","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:51:01.235017Z","pmid":"39741465","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":[]}