Some underarm odor arises when bacteria break down materials that are odorless when released onto the skin. Enzymes that cut molecules apart play a role along the way.
A 2024 study identified an enzyme called PepV in a species of skin bacterium that can carry out a previously unexplained breakdown step. It also suggests that, rather than being a specialized tool devoted solely to producing body odor, PepV is a broadly acting enzyme involved in ordinary nutrient utilization.
From an odor precursor to a pungent molecule
The study focused on Staphylococcus hominis, a bacterium also found on underarm skin. It takes up odorless precursors secreted by apocrine glands and converts them into 3M3SH, a strongly smelling sulfur-containing molecule.
The precursor is called Cys-Gly-3M3SH. The name may look complicated, but the important point here is that two amino acids, cysteine and glycine, are attached to the part that will become the odor molecule.
PatB, the enzyme responsible for the final step, can process Cys-3M3SH once glycine has been removed. It cannot act on the glycine-containing precursor. An earlier set of molecular “scissors” must therefore remove the glycine.
The uptake mechanism and the enzyme that finally releases the odor molecule had already been studied. This research aimed to identify the unexplained intermediate step and characterize the enzyme responsible.
Tracking the desired activity inside the bacterium
The researchers broke open S. hominis cells, extracted their proteins, and separated them through several stages using differences in their properties. At each stage, they looked for fractions retaining activity against the precursor.
To detect this activity, they also included PatB, the enzyme acting at the next step. If the enzyme being sought first removed glycine, PatB could then release 3M3SH. Measuring its production through a color change provided an indirect way to track the first enzyme’s activity.
Analysis of proteins in the active fractions identified PepV. The team then produced and purified PepV separately and confirmed that it acted on the precursor. Importantly, they did more than find it in an active sample: they verified the reaction of the isolated enzyme.
PepV alone does not directly release the odor molecule. The enzymes divide the work: PepV removes glycine, after which PatB releases the odor molecule.
Not dedicated solely to producing body odor
PepV is an enzyme that cleaves dipeptides, molecules consisting of two linked amino acids. The researchers tested its reactions with various dipeptides besides the body-odor precursor.
It acted broadly on the tested dipeptides containing L-amino acids. In contrast, under the tested conditions it did not cleave the tested D-amino-acid dipeptide D-Ala-D-Ala, which has a different spatial configuration, or the tripeptide L-Ala-L-Ala-L-Ala. This result alone does not establish that all combinations of two D-amino acids are resistant to cleavage. Rather than breaking down everything, it primarily handles substrates made of two amino acids.
It also efficiently processed a simple cysteine-glycine pair without the odor-forming group attached. Its catalytic efficiency, calculated from concentrations and reaction rates, was about 70 times higher than for the body-odor precursor. This comparison came from measurements of purified enzyme in vitro.
PepV from Staphylococcus aureus also carried out the same initial breakdown of the precursor. Because that bacterium lacks PatB, which performs the final step, this ability alone does not enable it to produce 3M3SH.
Together, the findings suggest that PepV can process the body-odor precursor as part of its broader role in helping bacteria utilize short peptides, rather than having evolved specifically for odor production. The glycine released during the reaction could also serve as material for bacterial protein and cell-wall synthesis.
Investigating a pocket that accommodates a bulky molecule
The body-odor precursor contains a bulkier group than ordinary dipeptides. How can PepV accommodate it?
Using a related enzyme with a known structure, the researchers built a three-dimensional model of S. hominis PepV. Placing the precursor in this model revealed a pocket beside the amino-acid binding region that appeared capable of accommodating the bulky odor-forming group.
To test this explanation, they replaced amino acids around the pocket. Changes that narrowed the space reduced activity, while some changes that enlarged it increased efficiency. The D437A substitution increased catalytic efficiency for the body-odor precursor about sixfold.
This supports a model in which space for accommodating the molecule contributes to the reaction. It was not a measurement showing “six times more body odor” in people. The structure was also a model based on related proteins, not a directly determined structure of S. hominis PepV bound to the precursor.
Metal ions also contributed to enzyme function, with manganese ions supporting the highest activity under the tested conditions. Both the shape that accommodates the molecule and the chemistry that drives the reaction are needed.
Understanding an odor pathway is not the same as demonstrating deodorization
This research filled in a missing part of the pathway by which S. hominis takes up an odorless material and breaks it down in two steps to produce 3M3SH. It also indicated that uptake and the initial breakdown recruit broadly used cellular functions, while the final PatB activity is more distinctive.
The experiments mainly used cell extracts and purified enzymes. They did not test a product that inhibits PepV on skin or remove its gene and demonstrate a reduction in human odor. The authors note that they could not fully reproduce the skin environment and leave open the possibility that other enzymes also contribute to this breakdown step.
Body odor also involves many molecules and microorganisms. This study identified one step in the pathway leading to 3M3SH. Reading it as progress in understanding odor mechanisms keeps its implications in proportion.
The research received funding from the UK’s BBSRC. The authors included a current Unilever employee and a researcher who worked for Unilever when the study was conducted, and those relationships were disclosed.
Summary
PepV removes glycine from an odorless body-odor precursor, preparing it for PatB to release the pungent molecule 3M3SH.
Its activity against many dipeptides, comparisons with an enzyme from another bacterial species, and structural modeling and mutation experiments suggest that this pathway uses a general bacterial nutrient-utilization mechanism rather than a system dedicated solely to body odor. Odor emerges from a chain linking secretions, microbes, and multiple enzymes. This study clarified one link in that chain.
References
Herman R, et al. Identification of a staphylococcal dipeptidase involved in the production of human body odor. Journal of Biological Chemistry. 2024;300(12):107928. doi:10.1016/j.jbc.2024.107928
