{"doi":"10.1016/j.jbc.2024.107928","title":"Identification of a staphylococcal dipeptidase involved in the production of human body odor","abstract":"The production of human body odor is the result of the action of commensal skin bacteria, including Staphylococcus hominis , acting to biotransform odorless apocrine gland secretions into volatile chemicals like thioalcohols such as 3-methyl-3-sulphanylhexan-1-ol (3M3SH). As the secreted odor precursor Cys-Gly-3M3SH contains a dipeptide, yet the final enzyme in the biotransformation pathway only functions on Cys-3M3SH, we sought to identify the remaining step in this human-adapted biochemical pathway using a novel coupled enzyme assay. Purification of this activity from S. hominis extracts led to the identification of the M20A-family PepV peptidase (ShPepV) as the primary Cys-Gly-3M3SH dipeptidase. To establish whether this was a primary substrate for PepV, the recombinant protein was purified and demonstrated broad activity against diverse dipeptides. The binding site for Cys-Gly-3M3SH was predicted using modeling, which suggested mutations that might accommodate this ligand more favorably. Indeed, a D437A resulted in an almost sixfold increase in the k cat /K m , whereas other introduced mutations reduced or abolished function. Together, these data identify an enzyme capable of catalyzing the missing step in an ancient human-specific biochemical transformation and suggest that the production of 3M3SH uses neither a dedicated transporter nor a peptidase for its breakdown, with only the final cleavage step, catalyzed by PatB cysteine-S-conjugate β-lyase, being a unique enzyme.","journal":"Journal of Biological Chemistry","year":2024,"id":456683,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"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":1281527,"name":"Bethan E. Kinniment-Williams","orcid":"0009-0001-9809-4134","position":1,"is_corresponding":false},{"id":1281528,"name":"Michelle Rudden","orcid":"0000-0001-9617-087X","position":2,"is_corresponding":false},{"id":1282013,"name":"Alexander Gordon James","orcid":null,"position":3,"is_corresponding":false},{"id":1281529,"name":"Anthony J. Wilkinson","orcid":"0000-0003-4577-9479","position":4,"is_corresponding":false},{"id":1281530,"name":"Barry Murphy","orcid":"0000-0003-2305-5875","position":5,"is_corresponding":false},{"id":1281531,"name":"Gavin H. Thomas","orcid":"0000-0002-9763-1313","position":6,"is_corresponding":false},{"id":1281526,"name":"Reyme Herman","orcid":"0000-0002-6620-3981","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:03:32.516678Z","pmid":"39454956","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":[]}