{"doi":"10.1002/ange.202005506","title":"Making and Breaking Leupeptin Protease Inhibitors in Pathogenic Gammaproteobacteria","abstract":"Abstract Leupeptin is a bacterial small molecule that is used worldwide as a protease inhibitor. However, its biosynthesis and genetic distribution remain unknown. We identified a family of leupeptins in gammaproteobacterial pathogens, including Photorhabdus , Xenorhabdus , and Klebsiella species, amongst others. Through genetic, metabolomic, and heterologous expression analyses, we established their construction by discretely expressed ligases and accessory enzymes. In Photorhabdus species, a hypothetical protein required for colonizing nematode hosts was established as a new class of proteases. This enzyme cleaved the tripeptide aldehyde protease inhibitors, leading to the formation of “pro‐pyrazinones” featuring a hetero‐tricyclic architecture. In Klebsiella oxytoca , the pathway was enriched in clinical isolates associated with respiratory tract infections. Thus, the bacterial production and proteolytic degradation of leupeptins can be associated with animal colonization phenotypes.","journal":"Angewandte Chemie","year":2020,"id":133841,"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":0,"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":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":393375,"name":"Joonseok Oh","orcid":"0000-0002-7616-1949","position":1,"is_corresponding":false},{"id":393376,"name":"Sabine Kienesberger","orcid":"0000-0003-3190-3678","position":2,"is_corresponding":false},{"id":393377,"name":"Nam Yoon Kim","orcid":"0009-0002-4719-9742","position":3,"is_corresponding":false},{"id":393378,"name":"David J. Clarke","orcid":"0000-0001-9082-0501","position":4,"is_corresponding":false},{"id":393379,"name":"Ellen L. Zechner","orcid":"0000-0003-2035-1898","position":5,"is_corresponding":false},{"id":304470,"name":"Jason M. Crawford","orcid":"0000-0002-7583-1242","position":6,"is_corresponding":false},{"id":394294,"name":"Jhe‐Hao Li","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:16:20.998822Z","pmid":null,"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":[]}