Herman, Reyme, Kinniment-Williams, Bethan, Rudden, Michelle orcid.org/0000-0001-9617-087X et al. (4 more authors) (2024) Identification of a staphylococcal dipeptidase involved in the production of human body odor. Journal of Biological Chemistry. 107928. ISSN 1083-351X
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 kcat/Km, 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Publisher Copyright: © 2024 The Authors |
Keywords: | Cys-Gly-3M3SH,enzyme kinetics,enzyme structure,malodor,metalloenzyme,peptidase,peptides,Staphylococcus hominis |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Jan 2025 11:40 |
Last Modified: | 02 Apr 2025 23:29 |
Published Version: | https://doi.org/10.1016/j.jbc.2024.107928 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.jbc.2024.107928 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221183 |
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Description: Identification of a staphylococcal dipeptidase involved in the production of human body odor
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