The Broadly Tuned Odorant Receptor OR1A1 is Highly Selective for 3-Methyl-2,4-nonanedione, a Key Food Odorant in Aged Wines, Tea, and Other Foods

Abstract

Key food odorants are the most relevant determinants by which we detect, recognize, and hedonically evaluate the aroma of foods and beverages. Odorants are detected by our chemical sense of olfaction, comprising a set of approximately 400 different odorant receptor types. However, the specific receptor activity patterns representing the aroma percepts of foods or beverages, as well as the key food odorant agonist profiles of single-odorant receptors, are largely unknown. We aimed to establish comprehensive key food odorant agonist profiles of 2 unrelated, broadly tuned receptors, OR1A1 and OR2W1, that had been associated thus far with mostly non-key food odorants and shared some of these agonists. By screening both receptors against 190 key food odorants in a cell-based luminescence assay, we identified 14 and 18 new key food odorant agonists for OR1A1 and OR2W1, respectively, with 3-methyl-2,4-nonanedione emerging as the most potent agonist for OR1A1 by 3 orders of magnitude, with a submicromolar half maximal effective concentration. 3-Methyl-2,4-nonanedione has been associated with a prune note in oxidized wine and is an aroma determinant in tea and apricots. Further screening against the entire set of 391 human odorant receptors revealed that 30 or 300 μmol/L 3-methyl-2,4-nonanedione activated only 1 receptor, OR1A1, suggesting a unique role of OR1A1 for the most sensitive detection of this key food odorant in wine, tea, and other food matrices.

The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

“…59,78 Other ORs were found to be more broadly tuned in their response to thiols and KFOs. 23a,71,79a When a family of 3-mercapto-2-methylalkan-1-ols were tested against OR2M3 using a cAMP luminescence assay, it was found that three substances with chain lengths C4–C6 activated OR2M3 in a specific and concentration-dependent manner. Homologues with C-atom chain lengths less than four and greater than six did not activate OR2M3.…”

“…21b Anosmics may still be able to “smell” ammonia, since their CN V may still be functioning, although in some cases with decreased sensitivity. 79b …”

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

“…The perception of odors of all kinds is initiated by binding to G protein-coupled receptors (GPCRs), encoded by about 400 odorant receptor (OR) genes [1][2][3], of which at least 270 appear to be expressed in the cilia of olfactory sensory neurons (OSNs) within the main olfactory epithelium (OE) of the nasal cavity [4]. Odor coding is then achieved in a combinatorial manner whereby more ORs are broadly tuned than narrowly tuned and whereby one odorant may activate multiple ORs [5][6][7][8][9][10][11][12][13][14].…”

“…Most of the thiol-responsive human ORs identified, so far are members of family 2 of ORs [5, 6, 11-13, 31, 49]. Recently, we identified one narrowly tuned thiol-responding human receptor, OR2M3, as well as two broadly tuned receptors with overlapping thiol agonist spectra [5,6]. One causative mechanism for differences in tuning breadth may be the size of the respective ligand-binding pockets.…”

“…Here, we investigated narrowly tuned OR2M3 with its agonist 3-mercapto-2-methylpentan-1-ol [6], a common and potent KFO from heated onions, which for thousands of years have been used worldwide as a food and in complementary medicine [51]. We compared OR2M3 with two most recently characterized broadly tuned receptors, OR2W1 and OR1A1, with three of their known agonists, 2-phenylethanethiol, 3-mercaptohexyl acetate, and allyl phenyl acetate [5], in a cell-based, online cAMP-luminescence GloSensor™ assay [52].…”