{"doi":"10.1021/jacs.4c18761","title":"Exquisite Complex Reaction Cascade in the Natural 1,2,4-Triazine Assembly","abstract":"1,2,4-Triazine ring is a scaffold widely found in biologically active compounds, but how nature makes it remains enigmatic. In this study, we unveil the complex enzymatic and nonenzymatic cascade reactions that assemble the 1,2,4-triazine moiety found in the structures of the natural products pseudoiodinine and toxoflavin. Through biochemical studies, isotope labeling, and the application of substrate analogues, we propose a plausible pathway for the 1,2,4-triazine assembly from a common precursor in riboflavin biosynthesis. This process involves four two-electron oxidation steps, C-N bond formation, decarboxylation, and the N-N bond forming step catalyzed by a metal-dependent WD40-repeat (WDR) protein. This study thus not only provides the first biocatalytic route for the 1,2,4-triazine assembly but also identifies a previously unrecognized catalytic role of a large WDR protein family.","journal":"Journal of the American Chemical Society","year":2025,"id":530578,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"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":1410227,"name":"Haoran Pang","orcid":"0000-0003-1604-5011","position":1,"is_corresponding":false},{"id":129844,"name":"Wenjun Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":1410226,"name":"Yiyuan Cheng","orcid":"0009-0006-9973-6211","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:51:05.836974Z","pmid":"40156852","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":[]}