OR2M3: A Highly Specific and Narrowly Tuned Human Odorant Receptor for the Sensitive Detection of Onion Key Food Odorant 3-Mercapto-2-methylpentan-1-ol

Abstract

The detection of key food odorants appears to be an important capability of odorant receptors. Here, thiols occupy an outstanding position among the 230 known key food odorants because of their very low odor thresholds. Members of the homologous series of 3-mercapto-2-methylalkan-1-ols have been described as onion key food odorants or food constituents and are detected at logarithmically different thresholds. 3-Mercapto-2-methylpentan-1-ol being the only key food odorant within this series also has the lowest odor threshold. Most odorants typically activate combinations of odorant receptors, which may be narrowly or broadly tuned. Consequently, a specific receptor activation pattern will define an odor quality. In contrast, here we show that just 1 of the 391 human odorant receptors, OR2M3, responded exclusively to 3-mercapto-2-methylpentan-1-ol of the 190 key food odorants tested, with a half maximal effective concentration at submicromolar concentration. Moreover, neither the Denisovan OR2M3 nor the closest OR2M3 homologs from five species did respond to this compound. This outstanding specificity of extremely narrowly tuned human OR2M3 can explain both odor qualities and odor threshold trend within a homologous series of 3-mercapto-2-methylalkan-1-ols and suggests a modern human-specific, food-related function of OR2M3 in detecting a single onion key food odorant.

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

“…Compounds related to 3-mercapto-2-methylpentan-1-ol, including 3-mercapto-2-methylbutan-1-ol and 3-mercapto-2-methylpropan-1-ol occur in beer, wine and hops. 77 It had been previously reported that both 1-octanethiol and 1-nonanethiol activate human ORs OR2C1, OR2W1, OR1A1, while 1-pentanethiol activates ORs OR2T2 and OR2T8. 59,78 Other ORs were found to be more broadly tuned in their response to thiols and KFOs.…”

“…76 By screening 3-mercapto-2-methylpentan-1-ol, a KFO found in onions having a characteristic onion odor, at either 30 or 300 μmol/L against 391 human ORs, Noe and coworkers found that OR2M3 was the only responder. 77 Furthermore, of 190 KFOs tested with OR2M3, 3-mercapto-2-methylpentan-1-ol was the only active ligand found. It is quite unusual for an odorant to activate only a single OR and for an OR to be so narrowly tuned in its response!…”

“…71 Recently a second human receptor, OR2M3, has been found, which responds strongly to thiols of slightly larger size than OR2T11. 77 These findings argue against there being a “large number of receptors” for thiols.…”

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].…”

“…Thiols play an outstanding role in human olfaction, for instance as body odor [15][16][17][18][19], environmental odors [20], and especially as key food odorants (KFOs), which appear in foods at concentrations above their odor threshold, and critically determine the aroma of foods [21]. Thiol odorants often show very low odor thresholds [6,[21][22][23][24][25]. The olfactory sensitivity for thiols is shown not only for humans but also for spider monkeys (Ateles geoffroyi), squirrel monkeys (Saimiri sciureus), and pigtail macaque (Macaca nemestrina) [26].…”