Chirality Matters - Enantioselective Orthologous Odorant Receptors for Related Terpenoid Structures

Humans can discriminate between a variety of enantiomeric odorants with different odor qualities, such as the spearmint-like (R)-(-)-carvone and the caraway-like (S)-(+)-carvone. Moreover, a specific anosmia for (R)-carvone, but not for (S)-carvone, was observed in 8% of the population. Recently, the odorant receptor OR1A1 has been identified to selectively respond to (R)-carvone over (S)-carvone. We screened 391 human odorant receptors (OR) versus (-)-menthone and (+)-menthone, and identified OR1A1 as best receptor for both menthone enantiomers. OR1A1 also responded to both, (S)-(-)-limonene and (R)-(+)-limonene. We compared potency and efficacy of the carvone, menthone, and limonene enantiomers on OR1A1 and on its orthologous receptor in chimpanzee. Both receptors differ in just three single nucleotide polymorphism(SNP)-affected amino acid positions, which in sum render the chimp receptor non-selective for the carvone enantiomers, and with a generally attenuated efficacy for terpenoids. Three other SNP-based single amino acid changes lead to either gain-of-function or loss-of-function OR1A1 phenotypes. Our data suggest OR1A1 haplotypes being involved in an enantioselective perception of terpenoids.