The molecular basis of thioalcohol production in human body odour

Abstract

Body odour is a characteristic trait of Homo sapiens, however its role in human behaviour and evolution is poorly understood. Remarkably, body odour is linked to the presence of a few species of commensal microbes. Herein we discover a bacterial enzyme, limited to odour-forming staphylococci that are able to cleave odourless precursors of thioalcohols, the most pungent components of body odour. We demonstrated using phylogenetics, biochemistry and structural biology that this cysteinethiol lyase (C-T lyase) is a PLP-dependent enzyme that moved horizontally into a unique monophyletic group of odour-forming staphylococci about 60 million years ago, and has subsequently tailored its enzymatic function to human-derived thioalcohol precursors. Significantly, transfer of this enzyme alone to non-odour producing staphylococci confers odour production, demonstrating that this C-T lyase is both necessary and sufficient for thioalcohol formation. The structure of the C-T lyase compared to that of other related enzymes reveals how the adaptation to thioalcohol precursors has evolved through changes in the binding site to create a constrained hydrophobic pocket that is selective for branched aliphatic thioalcohol ligands. The ancestral acquisition of this enzyme, and the subsequent evolution of the specificity for thioalcohol precursors implies that body odour production in humans is an ancient process. Human body odour is produced by bacterial transformation of odourless precursor molecules secreted onto the surface of the skin by apocrine glands 1-3. These glands are one of two major types of sweat gland found in Homo sapiens, the other being the eccrine glands. Eccrine glands are found in high density all over the body, they open directly onto the surface of the skin and are essential for thermoregulation 4 (Fig. 1A). In contrast, apocrine glands open into hair follicles and typically occur in high density at specific body sites (axilla [underarm], nipple and external genitalia) (Fig. 1A); their exact function and physiological role in modern humans remain poorly understood. The axillary microbiota plays an important role in the generation of human body odour. Staphylococcus, Cutibacterium (formerly Propionibacterium) and Corynebacterium are the dominant genera colonizing the axilla 5,6 , with recent metataxonomic studies highlighting the additional presence of Gram-positive anaerobic cocci (GPAC), notably Anaerococcus and Peptoniphilus species 5,7. Human axillary malodour is comprised of a mixture of volatile organic compounds with volatile fatty acids (VFAs) and thioalcohols being the primary components (Supplementary Information Figure S1) 8-10. Thioalcohols, despite being present in trace amounts, are the most pungent voaltiles 9. Natsch et al. 2,11 identified trace amounts of four different thioalcohols in axillary secretions with 3-methyl-3-sulfanylhexan-1-ol (3M3SH) being the most abundant. 3M3SH is generated from the odourless precursor Cys-Gly-3M3SH, an l-cysteinylglycine dipeptide-conjugated alcohol that is secr...

Shared volatile organic compounds between camel metabolic products elicits strong Stomoxys calcitrans attraction

“…Although, several chemical ecology studies have investigated different livestock and vector interactions that have enabled identification of attractants, and repellents 17,27,28 to the best of our knowledge this is the first study to compare the VOCs between metabolic products of the same animal. The distinct VOCs profiles observed between metabolic products suggest that VOC production in the camel may be driven by specific metabolic processes associated with microbes and tissue-specific enzymes 29 . Unlike animals, most VOCs research has been carried out on plants, but interestingly, the findings in the present are consistent with similar findings found for plants 30,31 .…”

“…The distinct VOCs profiles observed between metabolic products suggest that VOC production in the camel may be driven by specific metabolic processes associated with microbes and tissue-specific enzymes 29 . Unlike animals, most VOCs research has been carried out on plants, but interestingly, the findings in the present are consistent with similar findings found for plants 30 , 31 .…”

Infection threat shapes our social instincts

“…The MHC marks the scent of urine (both in mice and in humans: Eggert et al 1999) and is quite likely to affect the odor of one's breath, sweat, and genitals as well (Wobst 1999;Aksenov et al 2012;Grogan 2019). It can also alter the menagerie of microbes individuals carry around (Khan et al 2019), and thus the aromatic gases such microbes give off (Rudden et al 2020). Together, all these odors form a sort of olfactory fingerprint.…”

Real time observation of the interaction between aluminium salts and sweat under microfluidic conditions

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