{"doi":"10.1021/jacs.4c14573","title":"Single-Enzyme Conversion of Tryptophan to Skatole and Cyanide Expands the Mechanistic Competence of Diiron Oxidases","abstract":"High Resolution Image Download MS PowerPoint Slide Skatole is a pungent heterocyclic compound derived from the essential amino acid l -tryptophan by bacteria in the mammalian digestive tract. The four-step anaerobic conversion of tryptophan to skatole is well-established; though, to date, no aerobic counterpart has been reported. Herein, we report the discovery of the oxygen-dependent skatole synthase SktA that single-handedly converts 5-bromo- l -tryptophan to 5-bromoskatole, obviating the need for a multienzyme process. SktA is part of a three-gene biosynthetic gene cluster (BGC) in the cyanobacterium Nostoc punctiforme NIES-2108 and functions as a nonheme diiron enzyme belonging to the heme oxygenase-like domain-containing oxidase (HDO) superfamily. Our detailed biochemical analyses revealed cyanide and bicarbonate as biosynthetic coproducts, while stopped-flow experiments showed the hallmark formation of a substrate-triggered peroxo Fe 2 (III) intermediate. Overall, this work unravels an alternative pathway for converting tryptophan to skatole while also expanding the functional repertoire of HDO enzymes.","journal":"Journal of the American Chemical Society","year":2025,"id":511995,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"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":1045064,"name":"Logan A Calderone","orcid":"0000-0002-0960-3831","position":1,"is_corresponding":false},{"id":1371397,"name":"August Krueger","orcid":null,"position":2,"is_corresponding":false},{"id":471194,"name":"Maria‐Eirini Pandelia","orcid":"0000-0002-6750-1948","position":3,"is_corresponding":false},{"id":261966,"name":"Bradley S. Moore","orcid":"0000-0002-4652-1253","position":4,"is_corresponding":false},{"id":876382,"name":"Sanjoy Adak","orcid":"0000-0003-2889-4272","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:01.269605Z","pmid":"39939147","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":[]}