4.7 Article

An evolutionary conserved olfactory receptor for foodborne and semiochemical alkylpyrazines

期刊

FASEB JOURNAL
卷 35, 期 6, 页码 -

出版社

WILEY
DOI: 10.1096/fj.202100224R

关键词

chemical ecology; chemosensory evolution; odorant receptor; olfaction

资金

  1. Altria Client Services Inc, Richmond, VA, USA
  2. MARS Inc, McLean, VA, USA

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Molecular recognition plays a key role in biological systems, and the study of pyrazines has led to the discovery of OR5K1 as a specialized olfactory receptor across mammals for the detection of pyrazine-based key food odors and semiochemicals, indicating the significance of ecological evolution.
Molecular recognition is a fundamental principle in biological systems. The olfactory detection of both food and predators via ecological relevant odorant cues are abilities of eminent evolutionary significance for many species. Pyrazines are such volatile cues, some of which act as both human-centered key food odorants (KFOs) and semiochemicals. A pyrazine-selective odorant receptor has been elusive. Here we screened 2,3,5-trimethylpyrazine, a KFO and semiochemical, and 2,5-dihydro-2,4,5-trimethylthiazoline, an innate fear-associated non-KFO, against 616 human odorant receptor variants, in a cell-based luminescence assay. OR5K1 emerged as sole responding receptor. Tested against a comprehensive collection of 178 KFOs, we newly identified 18 pyrazines and (2R/2S)-4-methoxy-2,5-dimethylfuran-3(2H)-one as agonists. Notably, OR5K1 orthologs in mouse and domesticated species displayed a human-like, potency-ranked activation pattern of pyrazines, suggesting a domestication-led co-evolution of OR5K1 and its orthologs. In summary, OR5K1 is a specialized olfactory receptor across mammals for the detection of pyrazine-based key food odors and semiochemicals.

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