{"doi":"10.1021/jacs.4c04712","title":"Elucidation of Chalkophomycin Biosynthesis Reveals <i>N</i>-Hydroxypyrrole-Forming Enzymes","abstract":"High Resolution Image Download MS PowerPoint Slide Reactive functional groups, such as N -nitrosamines, impart unique bioactivities to the natural products in which they are found. Recent work has illuminated enzymatic N -nitrosation reactions in microbial natural product biosynthesis, motivating interest in discovering additional metabolites constructed using such reactivity. Here, we use a genome mining approach to identify over 400 cryptic biosynthetic gene clusters (BGCs) encoding homologues of the N -nitrosating biosynthetic enzyme SznF, including the BGC for chalkophomycin, a Cu II -binding metabolite that contains a C -type diazeniumdiolate and N -hydroxypyrrole. Characterizing chalkophomycin biosynthetic enzymes reveals previously unknown enzymes responsible for N -hydroxypyrrole biosynthesis, including the first prolyl- N -hydroxylase, and a key step in the assembly of the diazeniumdiolate-containing amino acid graminine. Discovery of this pathway enriches our understanding of the biosynthetic logic employed in constructing unusual heteroatom–heteroatom bond-containing functional groups, enabling future efforts in natural product discovery and biocatalysis.","journal":"Journal of the American Chemical Society","year":2024,"id":432268,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"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":1236841,"name":"Anika K. Chand","orcid":"0009-0006-3604-8550","position":1,"is_corresponding":false},{"id":1070440,"name":"Zheng Cui","orcid":"0000-0002-1503-7098","position":2,"is_corresponding":false},{"id":234900,"name":"Emily P. Balskus","orcid":"0000-0001-5985-5714","position":3,"is_corresponding":false},{"id":1236840,"name":"Anne Marie Crooke","orcid":"0000-0002-1581-6104","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T01:59:35.267142Z","pmid":"38810110","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":[]}