# Harnessing Odorant Receptor Activation to Suppress Real Malodor
## 1 Introduction  
There are various odors in our living environments. Recently, pet odors have become a significant problem in daily life. In particular, the smell of cat urine is strong. Thus, the development of deodorant for pets is progressing [1, 2, 3, 4]. Nevertheless, conventional methods, as described in previous studies, are often ineffective in open or large spaces [5]. Recently, sensory deodorization technology has been reported, which reduces malodor perception by suppressing the response of odorant receptors (ORs) to odor-causing substances [6]. While typical molecular components responsible for malodors include chemicals containing sulfur atoms, amine groups, and aldehyde groups, in reality, odors are complex mixtures of various volatile substances.  
ORs can be broadly categorized into canonical ORs [7, 8], trace-amine-associated receptors (TAARs) [9, 10], vomeronasal receptors [11, 12], and membrane-spanning 4A (MS4A) proteins [13]. Humans have approximately 400 canonical ORs, which belong to the G-protein-coupled receptor (GPCR) family and are characterized by seven transmembrane domains [7, 8, 14, 15, 16]. Canonical ORs are the primary sensor proteins for odor perception,selectively responding to various odor molecules [17; 18; 19]. TAARs, also a component of the GPCR family, primarily respond to amine compounds [9; 10]. Humans have six functional TAARs, whereas mice have 15. TAARs are less diverse than canonical ORs. Each mature olfactory sensory neuron expresses only one type of OR [10; 20; 21]. The combination codes generated by the responses of canonical ORs and TAARs make odor perception [22; 23]. Although odors are complex mixtures of various volatile substances, specific ORs play a key role in determining the perception of malodors. In particular, some ORs that respond to cat urine odors are believed to induce discomfort; therefore, inhibiting these receptors could suppress the perception of malodors.  
Cat urine contains a protein unique to cats, cauxin. Cauxin is an enzyme that hydrolyzes 3-methylbutanol-cysteineylglycine to filinine. Felinine is slowly degraded to 3-mercapto-3-methyl-1-butanol, which causes the specific smell of cat urine [24; 25]. However, cat urine odor is a complex mixture of several volatile organic compounds (VOCs) [26], and the VOC composition of cat urine changes over time [27]. Hence, screening for odor suppressors based on single compounds may overlook effective candidates constituting cat urine odor. Moreover, most ORs that probably respond to cat urine odor remain unidentified, and the number of potential receptor candidates is vast.  
As mentioned earlier, cat urine is a mixture of various substances. Testing deodorization strategies using the mixed odor is preferable to that focusing on single compounds. The composition of cat urine differs between individual cats depending on their living environment or diet. Even urine from a single cat varies in odor intensity with the collection day. Our goal was to identify compounds that could effectively suppress human perception of cat urine malodor based on high-throughput OR-expressing cell analysis. At first, we identified ORs that respond to the headspace gas of real cat urine (hereafter referred to as \"cat urine odor\"). Then, we screened for antagonistic fragrances that could inhibit these receptors.