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Today, axilla odours are socially stigmatized and are targeted with deodorants and antiperspirants representing a multi-billion market. Axilla odours aren't simple byproducts of our metabolism but specifically formed by an intricate interplay between i) specific glands, ii) secreted amino acid conjugates of highly specific odorants and iii) selective enzymes present in microorganisms colonizing our skin, providing a natural 'controlled-release' mechanism. Within a multidisciplinary research project, we were able to elucidate the structure of key body odorants, isolate and characterize secreted amino acid conjugates and identify the enzymes responsible for odour release. These enzymes then served as targets for the development of specific active compounds in an almost medicinal chemistry approach, an approach rarely used in the cosmetic field so far. Here we review the key new insights into the biochemistry of human body odour formation, with some remarks on the experimental steps undertaken and hurdles encountered. The development of deodorant actives and the difficult path to market for such specifically acting cosmetic actives is discussed. The basic insights into the biochemistry also opened the way to address some questions in population genetics: Why have large proportions of Asians lost the 'ability' to form body odours? Do twins smell the same? Are our typical body odours indeed influenced by the immune system as often claimed? After addressing these questions, I'll conclude with the key remaining challenges in this field on an ecological niche that is 'anatomically very close to our heart'.

Key human axilla malodorants are hexenoic acid (3) and 3-hydroxy-3-methyl-hexanoic acid (5), accompanied by some 25 structurally related hydroxyalkanoic acids and alkenoic acids. These sweat acids are secreted in the axilla in the form of odorless glutamine conjugates and are released upon enzymolysis by AMRE (Axillary Malodor Releasing Enzyme), produced by Corynebacteria. The sulfanylalkanols 8–11 represent another important group of axilla malodor compounds that are also secreted in the form of odorless precursors. The major precursors are cysteine–glycine sulfanylalkanol conjugates of type 14 and the minor precursors are cysteine sulfanylalkanol conjugates like 15. The release occurs upon action of a ?-lyase of axilla bacteria. Besides the classical approaches of axilla malodor masking using fragrances, the use of chemicals to neutralize malodorants is described. The elucidation of the biochemistry of the sweat acid release has allowed the development of fragrance precursors that act as competitive substrates to the natural malodor precursors as well as the development of specific antagonists that block AMRE. Finally, the characterization and functional expression of a first human malodor receptor presents an interesting approach for future development of axilla malodor blockers.