{"doi":"10.1002/anie.202502367","title":"A Ketone‐Accepting Pictet–Spenglerase for the Asymmetric Construction of 1,1‐Disubstituted Tetrahydro‐ß‐carboline Alkaloids","abstract":"In light of the ubiquity of 1,1'-disubstituted tetrahydro-ß-carboline (THBC) motif in alkaloid natural products, developing asymmetric methodology for its preparation is highly valuable. Despite the immense progress toward achieving stereoselective Pictet-Spengler reaction with aldehydes, the analogous reaction with ketones is still underdeveloped. Exploiting KslB, a Pictet-Spenglerase from the biosynthesis of kitasetaline, we develop a general, diastereoselective, and protecting-group free method for the construction of densely functionalized THBCs with α-quaternary center by coupling tryptophan derivatives and α-keto acids. We determine the stereochemistry of kitasetalic acid, KslB's physiological product and a key biosynthetic intermediate toward kitasetaline, and established that KslB's selectivity is opposite to what is achieved chemically. Our investigations of KslB show its high activity (total turnover number >438000), substrate promiscuity, and tolerance for high substrate concentrations (0.1 M). Additionally, a TrpB-KslB cascade enables the construction of complex tricyclic products from simple indoles in one-pot. X-ray structural characterization of KslB sheds light on potential active site interactions to account for its stereoselectivity and ability to accept ketone substrates.","journal":"Angewandte Chemie International Edition","year":2025,"id":530618,"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":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":1410580,"name":"Nour Wasfy","orcid":null,"position":1,"is_corresponding":false},{"id":1410258,"name":"Takahiro MORI","orcid":"0000-0002-0083-5062","position":2,"is_corresponding":false},{"id":1410259,"name":"Mien Van Hoang","orcid":"0009-0006-8847-9280","position":3,"is_corresponding":false},{"id":356900,"name":"Ikuro Abe","orcid":"0000-0002-3640-888X","position":4,"is_corresponding":false},{"id":568960,"name":"Hans Renata","orcid":"0000-0003-2468-2328","position":5,"is_corresponding":false},{"id":1410579,"name":"Ruiying Jiang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:51:05.836974Z","pmid":"40209176","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":[]}