ECRO XIX Trieste: “Towards musky odors: discovery of the new broadly tuned human musk receptor”

Musk odors have been used for medicine and fragrance from time immemorial because of their fascinating scent and potential effects on human health. The first natural musk, Muscone, originates from the musk deer where it has a pheromonal function. Nowadays, most of the musks used in the industry follows from chemical synthesis and are widely used in cosmetic and perfume industry due to their warmth, elegance, animal scent as well as for their fixative properties.

To date, four structurally diverse groups of chemical compounds sharing a musky-like note have been identified: nitro musks, polycyclic musks, macrocyclic musks and alicyclic (or linear) musks. Despite their big commercial success, the use of nitro and polycyclic musks has been reduced in recent years because of their potential health and environment damaging properties. Their replacement by safer and/or ecologically benign musks or compounds that enhance the musk perception remains an important goal.

In this study, we screened the human set of functional olfactory receptors (OR) for additional “musk” receptors and discovered a new unexpected OR belonging to class 2 activated by archetypal representatives of the four different groups of musk. So far, none of the formerly identified musk-receptors (OR5AN1 and OR11A1) showed such levels of responsiveness for all musk groups.  In this context, we have compared the selectivity, sensitivity and efficacy of these three receptors as well as the impact of amino acids mutations on the functionality of the receptor.  Given the importance of musk in our everyday life, the understanding of the molecular mechanisms that support the perception of the musky odor is crucial and will allow the development of new generation of musk compounds useful for perfumers and F&F companies.

Sandra Huysseune, Melodie Locrel, Alex Veithen, Magali Philippeau and Yannick Quesnel

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